CINXE.COM

<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <title>Atg8: an autophagy-related ubiquitin-like protein family | Genome Biology | Full Text</title> <meta name="citation_abstract" content="Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective."/> <meta name="journal_id" content="13059"/> <meta name="dc.title" content="Atg8: an autophagy-related ubiquitin-like protein family"/> <meta name="dc.source" content="Genome Biology 2011 12:7"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="BioMed Central"/> <meta name="dc.date" content="2011-07-27"/> <meta name="dc.type" content="ReviewPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2011 BioMed Central Ltd"/> <meta name="dc.rights" content="2011 BioMed Central Ltd"/> <meta name="dc.rightsAgent" content="reprints@biomedcentral.com"/> <meta name="dc.description" content="Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective."/> <meta name="prism.issn" content="1474-760X"/> <meta name="prism.publicationName" content="Genome Biology"/> <meta name="prism.publicationDate" content="2011-07-27"/> <meta name="prism.volume" content="12"/> <meta name="prism.number" content="7"/> <meta name="prism.section" content="ReviewPaper"/> <meta name="prism.startingPage" content="1"/> <meta name="prism.endingPage" content="11"/> <meta name="prism.copyright" content="2011 BioMed Central Ltd"/> <meta name="prism.rightsAgent" content="reprints@biomedcentral.com"/> <meta name="prism.url" content="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-7-226"/> <meta name="prism.doi" content="doi:10.1186/gb-2011-12-7-226"/> <meta name="citation_pdf_url" content="https://genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2011-12-7-226"/> <meta name="citation_fulltext_html_url" content="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-7-226"/> <meta name="citation_journal_title" content="Genome Biology"/> <meta name="citation_journal_abbrev" content="Genome Biol"/> <meta name="citation_publisher" content="BioMed Central"/> <meta name="citation_issn" content="1474-760X"/> <meta name="citation_title" content="Atg8: an autophagy-related ubiquitin-like protein family"/> <meta name="citation_volume" content="12"/> <meta name="citation_issue" content="7"/> <meta name="citation_publication_date" content="2011/07"/> <meta name="citation_online_date" content="2011/07/27"/> <meta name="citation_firstpage" content="1"/> <meta name="citation_lastpage" content="11"/> <meta name="citation_article_type" content="Protein family review"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1186/gb-2011-12-7-226"/> <meta name="DOI" content="10.1186/gb-2011-12-7-226"/> <meta name="size" content="343257"/> <meta name="citation_doi" content="10.1186/gb-2011-12-7-226"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1186/gb-2011-12-7-226&api_key="/> <meta name="description" content="Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective."/> <meta name="dc.creator" content="Shpilka, Tomer"/> <meta name="dc.creator" content="Weidberg, Hilla"/> <meta name="dc.creator" content="Pietrokovski, Shmuel"/> <meta name="dc.creator" content="Elazar, Zvulun"/> <meta name="dc.subject" content="Animal Genetics and Genomics"/> <meta name="dc.subject" content="Human Genetics"/> <meta name="dc.subject" content="Plant Genetics and Genomics"/> <meta name="dc.subject" content="Microbial Genetics and Genomics"/> <meta name="dc.subject" content="Bioinformatics"/> <meta name="dc.subject" content="Evolutionary Biology"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=The genome sequence of Schizosaccharomyces pombe; citation_author=V Wood, R Gwilliam, MA Rajandream, M Lyne, R Lyne, A Stewart, J Sgouros, N Peat, J Hayles, S Baker, D Basham, S Bowman, K Brooks, D Brown, S Brown, T Chillingworth, C Churcher, M Collins, R Connor, A Cronin, P Davis, T Feltwell, A Fraser, S Gentles, A Goble, N Hamlin, D Harris, J Hidalgo, G Hodgson, S Holroyd; citation_volume=415; citation_publication_date=2002; citation_pages=871-880; citation_id=CR1"/> <meta name="citation_reference" content="VectorBase: I. scapularis. [ http://iscapularis.vectorbase.org/ ]"/> <meta name="citation_reference" content="Insights into social insects from the genome of the honeybee Apis mellifera. Nature. 2006, 443: 931-949. 10.1038/nature05260."/> <meta name="citation_reference" content="A Database of Drosophila Genes & Genomes. [ http://flybase.org/ ]"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=The Amphimedon queenslandica genome and the evolution of animal complexity; citation_author=M Srivastava, O Simakov, J Chapman, B Fahey, ME Gauthier, T Mitros, GS Richards, C Conaco, M Dacre, U Hellsten, C Larroux, NH Putnam, M Stanke, M Adamska, A Darling, SM Degnan, TH Oakley, DC Plachetzki, Y Zhai, M Adamski, A Calcino, SF Cummins, DM Goodstein, C Harris, DJ Jackson, SP Leys, S Shu, BJ Woodcroft, M Vervoort, KS Kosik; citation_volume=466; citation_publication_date=2010; citation_pages=720-726; citation_id=CR5"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans; citation_author=N King, MJ Westbrook, SL Young, A Kuo, M Abedin, J Chapman, S Fairclough, U Hellsten, Y Isogai, I Letunic, M Marr, D Pincus, N Putnam, A Rokas, KJ Wright, R Zuzow, W Dirks, M Good, D Goodstein, D Lemons, W Li, JB Lyons, A Morris, S Nichols, DJ Richter, A Salamov, JG Sequencing, P Bork, WA Lim, G Manning; citation_volume=451; citation_publication_date=2008; citation_pages=783-788; citation_id=CR6"/> <meta name="citation_reference" content="citation_journal_title=J Exp Bot; citation_title=The autophagy-associated Atg8 gene family operates both under favorable growth conditions and under starvation stresses in Arabidopsis plants; citation_author=S Sláviková, G Shy, Y Yao, R Glozman, H Levanony, S Pietrokovski, Z Elazar, G Galili; citation_volume=56; citation_publication_date=2005; citation_pages=2839-2849; citation_id=CR7"/> <meta name="citation_reference" content="citation_journal_title=Neuron; citation_title=Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding; citation_author=JE Coyle, S Qamar, KR Rajashankar, DB Nikolov; citation_volume=33; citation_publication_date=2002; citation_pages=63-74; citation_id=CR8"/> <meta name="citation_reference" content="citation_journal_title=Acta Crystallogr Sect F Struct Biol Cryst Commun; citation_title=Structure of autophagy-related protein Atg8 from the silkworm Bombyx mori; citation_author=C Hu, X Zhang, YB Teng, HX Hu, WF Li; citation_volume=66; citation_publication_date=2010; citation_pages=787-790; citation_id=CR9"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=Trypanosoma brucei ATG8: structural insights into autophagic-like mechanisms in protozoa; citation_author=R Koopmann, K Muhammad, M Perbandt, C Betzel, M Duszenko; citation_volume=5; citation_publication_date=2009; citation_pages=1085-1091; citation_id=CR10"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains; citation_author=T Kouno, M Mizuguchi, I Tanida, T Ueno, T Kanematsu, Y Mori, H Shinoda, M Hirata, E Kominami, K Kawano; citation_volume=280; citation_publication_date=2005; citation_pages=24610-24617; citation_id=CR11"/> <meta name="citation_reference" content="citation_journal_title=J Biomol NMR; citation_title=The NMR structure of the autophagy-related protein Atg8; citation_author=H Kumeta, M Watanabe, H Nakatogawa, M Yamaguchi, K Ogura, W Adachi, Y Fujioka, NN Noda, Y Ohsumi, F Inagaki; citation_volume=47; citation_publication_date=2010; citation_pages=237-241; citation_id=CR12"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p; citation_author=Y Paz, Z Elazar, D Fass; citation_volume=275; citation_publication_date=2000; citation_pages=25445-25450; citation_id=CR13"/> <meta name="citation_reference" content="citation_journal_title=Biochem Biophys Res Commun; citation_title=Solution structure of Atg8 reveals conformational polymorphism of the N-terminal domain; citation_author=M Schwarten, M Stoldt, J Mohrluder, D Willbold; citation_volume=395; citation_publication_date=2010; citation_pages=426-431; citation_id=CR14"/> <meta name="citation_reference" content="citation_journal_title=Genes Cells; citation_title=The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8; citation_author=K Sugawara, NN Suzuki, Y Fujioka, N Mizushima, Y Ohsumi, F Inagaki; citation_volume=9; citation_publication_date=2004; citation_pages=611-618; citation_id=CR15"/> <meta name="citation_reference" content="citation_journal_title=Chem Rev; citation_title=ATG systems from the protein structural point of view; citation_author=NN Noda, Y Ohsumi, F Inagaki; citation_volume=109; citation_publication_date=2009; citation_pages=1587-1598; citation_id=CR16"/> <meta name="citation_reference" content="citation_journal_title=EMBO Rep; citation_title=Crystal structure of the GABA(A)-receptor-associated protein, GABARAP; citation_author=VN Bavro, M Sola, A Bracher, M Kneussel, H Betz, W Weissenhorn; citation_volume=3; citation_publication_date=2002; citation_pages=183-189; citation_id=CR17"/> <meta name="citation_reference" content="citation_journal_title=Annu Rev Biochem; citation_title=Biogenesis and cargo selectivity of autophagosomes; citation_author=H Weidberg, E Shvets, Z Elazar; citation_volume=80; citation_publication_date=2011; citation_pages=125-156; citation_id=CR18"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy; citation_author=Y Ichimura, Y Imamura, K Emoto, M Umeda, T Noda, Y Ohsumi; citation_volume=279; citation_publication_date=2004; citation_pages=40584-40592; citation_id=CR19"/> <meta name="citation_reference" content="citation_journal_title=Cell; citation_title=Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion; citation_author=H Nakatogawa, Y Ichimura, Y Ohsumi; citation_volume=130; citation_publication_date=2007; citation_pages=165-178; citation_id=CR20"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes; citation_author=E Shvets, A Abada, H Weidberg, Z Elazar; citation_volume=7; citation_publication_date=2011; citation_pages=683-688; citation_id=CR21"/> <meta name="citation_reference" content="citation_journal_title=Dev Cell; citation_title=LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis; citation_author=H Weidberg, T Shpilka, E Shvets, A Abada, F Shimron, Z Elazar; citation_volume=20; citation_publication_date=2011; citation_pages=444-454; citation_id=CR22"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B; citation_author=H He, Y Dang, F Dai, Z Guo, J Wu, X She, Y Pei, Y Chen, W Ling, C Wu, S Zhao, JO Liu, L Yu; citation_volume=278; citation_publication_date=2003; citation_pages=29278-29287; citation_id=CR23"/> <meta name="citation_reference" content="citation_journal_title=Genomics; citation_title=Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein; citation_author=Y Xin, L Yu, Z Chen, L Zheng, Q Fu, J Jiang, P Zhang, R Gong, S Zhao; citation_volume=74; citation_publication_date=2001; citation_pages=408-413; citation_id=CR24"/> <meta name="citation_reference" content="citation_journal_title=Brain Res Mol Brain Res; citation_title=Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system; citation_author=C Nemos, V Mansuy, S Vernier-Magnin, A Fraichard, M Jouvenot, R Delage-Mourroux; citation_volume=119; citation_publication_date=2003; citation_pages=216-219; citation_id=CR25"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28; citation_author=Y Sagiv, A Legesse-Miller, A Porat, Z Elazar; citation_volume=19; citation_publication_date=2000; citation_pages=1494-1504; citation_id=CR26"/> <meta name="citation_reference" content="citation_journal_title=Biochem Biophys Res Commun; citation_title=Induced expressions of Rab24 GTPase and LC3 in nerve-injured motor neurons; citation_author=Y Egami, S Kiryu-Seo, T Yoshimori, H Kiyama; citation_volume=337; citation_publication_date=2005; citation_pages=1206-1213; citation_id=CR27"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Formation process of autophagosome is traced with Apg8/Aut7p in yeast; citation_author=T Kirisako, M Baba, N Ishihara, K Miyazawa, M Ohsumi, T Yoshimori, T Noda, Y Ohsumi; citation_volume=147; citation_publication_date=1999; citation_pages=435-446; citation_id=CR28"/> <meta name="citation_reference" content="citation_journal_title=Biochem Biophys Res Commun; citation_title=Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine; citation_author=CE Zois, A Giatromanolaki, H Kainulainen, S Botaitis, S Torvinen, C Simopoulos, A Kortsaris, E Sivridis, MI Koukourakis; citation_volume=404; citation_publication_date=2011; citation_pages=552-558; citation_id=CR29"/> <meta name="citation_reference" content="citation_journal_title=BMC Genomics; citation_title=Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis; citation_author=T van Zutphen, RJ Baerends, KA Susanna, A de Jong, OP Kuipers, M Veenhuis, IJ van der Klei; citation_volume=11; citation_publication_date=2010; citation_pages=1; citation_id=CR30"/> <meta name="citation_reference" content="citation_journal_title=Cell Metab; citation_title=FoxO3 controls autophagy in skeletal muscle in vivo; citation_author=C Mammucari, G Milan, V Romanello, E Masiero, R Rudolf, P Del Piccolo, SJ Burden, R Di Lisi, C Sandri, J Zhao, AL Goldberg, S Schiaffino, M Sandri; citation_volume=6; citation_publication_date=2007; citation_pages=458-471; citation_id=CR31"/> <meta name="citation_reference" content="citation_journal_title=Oncogene; citation_title=E2F1 regulates autophagy and the transcription of autophagy genes; citation_author=S Polager, M Ofir, D Ginsberg; citation_volume=27; citation_publication_date=2008; citation_pages=4860-4864; citation_id=CR32"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=FoxO transcription factors promote autophagy in cardiomyocytes; citation_author=A Sengupta, JD Molkentin, KE Yutzey; citation_volume=284; citation_publication_date=2009; citation_pages=28319-28331; citation_id=CR33"/> <meta name="citation_reference" content="citation_journal_title=Cell Metab; citation_title=FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells; citation_author=J Zhao, JJ Brault, A Schild, P Cao, M Sandri, S Schiaffino, SH Lecker, AL Goldberg; citation_volume=6; citation_publication_date=2007; citation_pages=472-483; citation_id=CR34"/> <meta name="citation_reference" content="citation_journal_title=Biochim Biophys Acta; citation_title=Involvement of LMA1 and GATE-16 family members in intracellular membrane dynamics; citation_author=Z Elazar, R Scherz-Shouval, H Shorer; citation_volume=1641; citation_publication_date=2003; citation_pages=145-156; citation_id=CR35"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Isolation and characterization of a novel low molecular weight protein involved in intra-Golgi traffic; citation_author=A Legesse-Miller, Y Sagiv, A Porat, Z Elazar; citation_volume=273; citation_publication_date=1998; citation_pages=3105-3109; citation_id=CR36"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion; citation_author=JM Muller, J Shorter, R Newman, K Deinhardt, Y Sagiv, Z Elazar, G Warren, DT Shima; citation_volume=157; citation_publication_date=2002; citation_pages=1161-1173; citation_id=CR37"/> <meta name="citation_reference" content="citation_journal_title=FEBS Lett; citation_title=18 kDa microtubule-associated protein: identification as a new light chain (LC-3) of microtubule-associated protein 1 (MAP-1); citation_author=SA Kuznetsov, VI Gelfand; citation_volume=212; citation_publication_date=1987; citation_pages=145-148; citation_id=CR38"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B; citation_author=SS Mann, JA Hammarback; citation_volume=269; citation_publication_date=1994; citation_pages=11492-11497; citation_id=CR39"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton; citation_author=H Wang, FK Bedford, NJ Brandon, SJ Moss, RW Olsen; citation_volume=397; citation_publication_date=1999; citation_pages=69-72; citation_id=CR40"/> <meta name="citation_reference" content="citation_journal_title=J Neurosci; citation_title=GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons; citation_author=TA Leil, ZW Chen, CS Chang, RW Olsen; citation_volume=24; citation_publication_date=2004; citation_pages=11429-11438; citation_id=CR41"/> <meta name="citation_reference" content="citation_journal_title=J Neurosci; citation_title=C-terminal modification is required for GABARAP-mediated GABA(A) receptor trafficking; citation_author=ZW Chen, CS Chang, TA Leil, RW Olsen; citation_volume=27; citation_publication_date=2007; citation_pages=6655-6663; citation_id=CR42"/> <meta name="citation_reference" content="citation_journal_title=FEBS Lett; citation_title=Association of human transferrin receptor with GABARAP; citation_author=F Green, T O'Hare, A Blackwell, CA Enns; citation_volume=518; citation_publication_date=2002; citation_pages=101-106; citation_id=CR43"/> <meta name="citation_reference" content="citation_journal_title=Genes Dev; citation_title=PX-RICS mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex; citation_author=T Nakamura, T Hayashi, Y Nasu-Nishimura, F Sakaue, Y Morishita, T Okabe, S Ohwada, K Matsuura, T Akiyama; citation_volume=22; citation_publication_date=2008; citation_pages=1244-1256; citation_id=CR44"/> <meta name="citation_reference" content="citation_journal_title=Mol Cell Neurosci; citation_title=The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors; citation_author=JT Kittler, P Rostaing, G Schiavo, JM Fritschy, R Olsen, A Triller, SJ Moss; citation_volume=18; citation_publication_date=2001; citation_pages=13-25; citation_id=CR45"/> <meta name="citation_reference" content="citation_journal_title=Proc Natl Acad Sci USA; citation_title=The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics; citation_author=L Chen, H Wang, S Vicini, RW Olsen; citation_volume=97; citation_publication_date=2000; citation_pages=11557-11562; citation_id=CR46"/> <meta name="citation_reference" content="citation_journal_title=J Neurochem; citation_title=Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction; citation_author=H Wang, RW Olsen; citation_volume=75; citation_publication_date=2000; citation_pages=644-655; citation_id=CR47"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor; citation_author=C Chen, JG Li, Y Chen, P Huang, Y Wang, LY Liu-Chen; citation_volume=281; citation_publication_date=2006; citation_pages=7983-7993; citation_id=CR48"/> <meta name="citation_reference" content="citation_journal_title=Biochem Biophys Res Commun; citation_title=GEC1, a protein related to GABARAP, interacts with tubulin and GABA(A) receptor; citation_author=V Mansuy, W Boireau, A Fraichard, JL Schlick, M Jouvenot, R Delage-Mourroux; citation_volume=325; citation_publication_date=2004; citation_pages=639-648; citation_id=CR49"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Effects of C-terminal modifications of GEC1 Protein and {gamma}-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP), two microtubule-associated proteins, on {kappa} opioid receptor expression; citation_author=C Chen, Y Wang, P Huang, LY Liu-Chen; citation_volume=286; citation_publication_date=2011; citation_pages=15106-15115; citation_id=CR50"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect; citation_author=Y Chen, C Chen, E Kotsikorou, DL Lynch, PH Reggio, LY Liu-Chen; citation_volume=284; citation_publication_date=2009; citation_pages=1673-1685; citation_id=CR51"/> <meta name="citation_reference" content="citation_journal_title=J Cell Sci; citation_title=Atg8 regulates vacuolar membrane dynamics in a lipidation-independent manner in Pichia pastoris; citation_author=N Tamura, M Oku, Y Sakai; citation_volume=123; citation_publication_date=2010; citation_pages=4107-4116; citation_id=CR52"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes; citation_author=A Legesse-Miller, Y Sagiv, R Glozman, Z Elazar; citation_volume=275; citation_publication_date=2000; citation_pages=32966-32973; citation_id=CR53"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway; citation_author=TM Harding, KA Morano, SV Scott, DJ Klionsky; citation_volume=131; citation_publication_date=1995; citation_pages=591-602; citation_id=CR54"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=Aut2p and Aut7p, two novel microtubule-associated proteins are essential for delivery of autophagic vesicles to the vacuole; citation_author=T Lang, E Schaeffeler, D Bernreuther, M Bredschneider, DH Wolf, M Thumm; citation_volume=17; citation_publication_date=1998; citation_pages=3597-3607; citation_id=CR55"/> <meta name="citation_reference" content="citation_journal_title=Proc Natl Acad Sci USA; citation_title=Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole; citation_author=SV Scott, A Hefner-Gravink, KA Morano, T Noda, Y Ohsumi, DJ Klionsky; citation_volume=93; citation_publication_date=1996; citation_pages=12304-12308; citation_id=CR56"/> <meta name="citation_reference" content="citation_journal_title=FEBS Lett; citation_title=The Cvt pathway as a model for selective autophagy; citation_author=MA Lynch-Day, DJ Klionsky; citation_volume=584; citation_publication_date=2010; citation_pages=1359-1366; citation_id=CR57"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p; citation_author=K Suzuki, C Kondo, M Morimoto, Y Ohsumi; citation_volume=285; citation_publication_date=2010; citation_pages=30019-30025; citation_id=CR58"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways; citation_author=WP Huang, SV Scott, J Kim, DJ Klionsky; citation_volume=275; citation_publication_date=2000; citation_pages=5845-5851; citation_id=CR59"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex; citation_author=J Kim, WP Huang, DJ Klionsky; citation_volume=152; citation_publication_date=2001; citation_pages=51-64; citation_id=CR60"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway; citation_author=T Kirisako, Y Ichimura, H Okada, Y Kabeya, N Mizushima, T Yoshimori, M Ohsumi, T Takao, T Noda, Y Ohsumi; citation_volume=151; citation_publication_date=2000; citation_pages=263-276; citation_id=CR61"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy; citation_author=I Tanida, N Mizushima, M Kiyooka, M Ohsumi, T Ueno, Y Ohsumi, E Kominami; citation_volume=10; citation_publication_date=1999; citation_pages=1367-1379; citation_id=CR62"/> <meta name="citation_reference" content="citation_journal_title=J Bacteriol; citation_title=AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae; citation_author=M Schlumpberger, E Schaeffeler, M Straub, M Bredschneider, DH Wolf, M Thumm; citation_volume=179; citation_publication_date=1997; citation_pages=1068-1076; citation_id=CR63"/> <meta name="citation_reference" content="citation_journal_title=Nature; citation_title=A ubiquitin-like system mediates protein lipidation; citation_author=Y Ichimura, T Kirisako, T Takao, Y Satomi, Y Shimonishi, N Ishihara, N Mizushima, I Tanida, E Kominami, M Ohsumi, T Noda, Y Ohsumi; citation_volume=408; citation_publication_date=2000; citation_pages=488-492; citation_id=CR64"/> <meta name="citation_reference" content="citation_journal_title=FEBS Lett; citation_title=Current knowledge of the pre-autophagosomal structure (PAS); citation_author=K Suzuki, Y Ohsumi; citation_volume=584; citation_publication_date=2010; citation_pages=1280-1286; citation_id=CR65"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation; citation_author=K Suzuki, T Kirisako, Y Kamada, N Mizushima, T Noda, Y Ohsumi; citation_volume=20; citation_publication_date=2001; citation_pages=5971-5981; citation_id=CR66"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy; citation_author=T Hanada, NN Noda, Y Satomi, Y Ichimura, Y Fujioka, T Takao, F Inagaki, Y Ohsumi; citation_volume=282; citation_publication_date=2007; citation_pages=37298-37302; citation_id=CR67"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Dissection of autophagosome biogenesis into distinct nucleation and expansion steps; citation_author=H Abeliovich, WA Dunn, J Kim, DJ Klionsky; citation_volume=151; citation_publication_date=2000; citation_pages=1025-1034; citation_id=CR68"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=Atg8 controls phagophore expansion during autophagosome formation; citation_author=Z Xie, U Nair, DJ Klionsky; citation_volume=19; citation_publication_date=2008; citation_pages=3290-3298; citation_id=CR69"/> <meta name="citation_reference" content="citation_journal_title=EMBO Rep; citation_title=Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy; citation_author=N Amar, G Lustig, Y Ichimura, Y Ohsumi, Z Elazar; citation_volume=7; citation_publication_date=2006; citation_pages=635-642; citation_id=CR70"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function; citation_author=KH Ho, HE Chang, WP Huang; citation_volume=5; citation_publication_date=2009; citation_pages=461-471; citation_id=CR71"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8; citation_author=R Krick, S Bremer, E Welter, P Schlotterhose, Y Muehe, EL Eskelinen, M Thumm; citation_volume=190; citation_publication_date=2010; citation_pages=965-973; citation_id=CR72"/> <meta name="citation_reference" content="citation_title=GABARAPL1 (GEC1) associates with autophagic vesicles; citation_inbook_title=Autophagy; citation_publication_date=2010; citation_id=CR73; citation_author=FZ Chakrama; citation_author=S Seguin-Py; citation_author=JN Le Grand; citation_author=A Fraichard; citation_author=R Delage-Mourroux; citation_author=G Despouy; citation_author=V Perez; citation_author=M Jouvenot; citation_author=M Boyer-Guittaut"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing; citation_author=Y Kabeya, N Mizushima, T Ueno, A Yamamoto, T Kirisako, T Noda, E Kominami, Y Ohsumi, T Yoshimori; citation_volume=19; citation_publication_date=2000; citation_pages=5720-5728; citation_id=CR74"/> <meta name="citation_reference" content="citation_journal_title=J Cell Sci; citation_title=LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation; citation_author=Y Kabeya, N Mizushima, A Yamamoto, S Oshitani-Okamoto, Y Ohsumi, T Yoshimori; citation_volume=117; citation_publication_date=2004; citation_pages=2805-2812; citation_id=CR75"/> <meta name="citation_reference" content="citation_journal_title=Int J Biochem Cell Biol; citation_title=LC3 conjugation system in mammalian autophagy; citation_author=I Tanida, T Ueno, E Kominami; citation_volume=36; citation_publication_date=2004; citation_pages=2503-2518; citation_id=CR76"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy; citation_author=N Fujita, T Itoh, H Omori, M Fukuda, T Noda, T Yoshimori; citation_volume=19; citation_publication_date=2008; citation_pages=2092-2100; citation_id=CR77"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L; citation_author=J Hemelaar, VS Lelyveld, BM Kessler, HL Ploegh; citation_volume=278; citation_publication_date=2003; citation_pages=51841-51850; citation_id=CR78"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes; citation_author=I Tanida, T Ueno, E Kominami; citation_volume=279; citation_publication_date=2004; citation_pages=47704-47710; citation_id=CR79"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates; citation_author=M Li, Y Hou, J Wang, X Chen, ZM Shao, XM Yin; citation_volume=286; citation_publication_date=2011; citation_pages=7327-7338; citation_id=CR80"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A; citation_author=R Scherz-Shouval, Y Sagiv, H Shorer, Z Elazar; citation_volume=278; citation_publication_date=2003; citation_pages=14053-14058; citation_id=CR81"/> <meta name="citation_reference" content="citation_journal_title=J Cell Sci; citation_title=Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis; citation_author=VM Betin, JD Lane; citation_volume=122; citation_publication_date=2009; citation_pages=2554-2566; citation_id=CR82"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4; citation_author=R Scherz-Shouval, E Shvets, E Fass, H Shorer, L Gil, Z Elazar; citation_volume=26; citation_publication_date=2007; citation_pages=1749-1760; citation_id=CR83"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker; citation_author=N Mizushima, A Yamamoto, M Matsui, T Yoshimori, Y Ohsumi; citation_volume=15; citation_publication_date=2004; citation_pages=1101-1111; citation_id=CR84"/> <meta name="citation_reference" content="citation_journal_title=Methods Mol Biol; citation_title=Measurement of autophagy in cells and tissues; citation_author=I Tanida, S Waguri; citation_volume=648; citation_publication_date=2010; citation_pages=193-214; citation_id=CR85"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure; citation_author=N Fujita, M Hayashi-Nishino, H Fukumoto, H Omori, A Yamamoto, T Noda, T Yoshimori; citation_volume=19; citation_publication_date=2008; citation_pages=4651-4659; citation_id=CR86"/> <meta name="citation_reference" content="citation_journal_title=Nat Cell Biol; citation_title=A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation; citation_author=M Hayashi-Nishino, N Fujita, T Noda, A Yamaguchi, T Yoshimori, A Yamamoto; citation_volume=11; citation_publication_date=2009; citation_pages=1433-1437; citation_id=CR87"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice; citation_author=YS Sou, S Waguri, J Iwata, T Ueno, T Fujimura, T Hara, N Sawada, A Yamada, N Mizushima, Y Uchiyama, E Kominami, K Tanaka, M Komatsu; citation_volume=19; citation_publication_date=2008; citation_pages=4762-4775; citation_id=CR88"/> <meta name="citation_reference" content="citation_journal_title=EMBO J; citation_title=LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis; citation_author=H Weidberg, E Shvets, T Shpilka, F Shimron, V Shinder, Z Elazar; citation_volume=29; citation_publication_date=2010; citation_pages=1792-1802; citation_id=CR89"/> <meta name="citation_reference" content="citation_journal_title=EMBO Rep; citation_title=The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells; citation_author=C Mauvezin, M Orpinell, VA Francis, F Mansilla, J Duran, V Ribas, M Palacin, P Boya, AA Teleman, A Zorzano; citation_volume=11; citation_publication_date=2010; citation_pages=37-44; citation_id=CR90"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Cell; citation_title=The TP53INP2 protein is required for autophagy in mammalian cells; citation_author=J Nowak, C Archange, J Tardivel-Lacombe, P Pontarotti, MJ Pebusque, MI Vaccaro, G Velasco, JC Dagorn, JL Iovanna; citation_volume=20; citation_publication_date=2009; citation_pages=870-881; citation_id=CR91"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Regulation of autophagy by the p300 acetyltransferase; citation_author=IH Lee, T Finkel; citation_volume=284; citation_publication_date=2009; citation_pages=6322-6328; citation_id=CR92"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Regulation of the autophagy protein LC3 by phosphorylation; citation_author=SJ Cherra, SM Kulich, G Uechi, M Balasubramani, J Mountzouris, BW Day, CT Chu; citation_volume=190; citation_publication_date=2010; citation_pages=533-539; citation_id=CR93"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death; citation_author=G Bjorkoy, T Lamark, A Brech, H Outzen, M Perander, A Overvatn, H Stenmark, T Johansen; citation_volume=171; citation_publication_date=2005; citation_pages=603-614; citation_id=CR94"/> <meta name="citation_reference" content="citation_journal_title=Mol Cell; citation_title=A role for NBR1 in autophagosomal degradation of ubiquitinated substrates; citation_author=V Kirkin, T Lamark, YS Sou, G Bjørkøy, JL Nunn, JA Bruun, E Shvets, DG McEwan, TH Clausen, P Wild, I Bilusic, JP Theurillat, A Øvervatn, T Ishii, Z Elazar, M Komatsu, I Dikic, T Johansen; citation_volume=33; citation_publication_date=2009; citation_pages=505-516; citation_id=CR95"/> <meta name="citation_reference" content="citation_journal_title=EMBO Rep; citation_title=Nix is a selective autophagy receptor for mitochondrial clearance; citation_author=I Novak, V Kirkin, DG McEwan, J Zhang, P Wild, A Rozenknop, V Rogov, F Löhr, D Popovic, A Occhipinti, AS Reichert, J Terzic, V Dötsch, PA Ney, I Dikic; citation_volume=11; citation_publication_date=2010; citation_pages=45-51; citation_id=CR96"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy; citation_author=M Schwarten, J Mohrluder, P Ma, M Stoldt, Y Thielmann, T Stangler, N Hersch, B Hoffmann, R Merkel, D Willbold; citation_volume=5; citation_publication_date=2009; citation_pages=690-698; citation_id=CR97"/> <meta name="citation_reference" content="citation_journal_title=J Cell Biol; citation_title=Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease; citation_author=M Filimonenko, S Stuffers, C Raiborg, A Yamamoto, L Malerod, EM Fisher, A Isaacs, A Brech, H Stenmark, A Simonsen; citation_volume=179; citation_publication_date=2007; citation_pages=485-500; citation_id=CR98"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy; citation_author=TH Clausen, T Lamark, P Isakson, K Finley, KB Larsen, A Brech, A Øvervatn, H Stenmark, G Bjørkøy, A Simonsen, T Johansen; citation_volume=6; citation_publication_date=2010; citation_pages=330-344; citation_id=CR99"/> <meta name="citation_reference" content="citation_journal_title=Mol Cell; citation_title=The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy; citation_author=M Filimonenko, P Isakson, KD Finley, M Anderson, H Jeong, TJ Melia, BJ Bartlett, KM Myers, HC Birkeland, T Lamark, D Krainc, A Brech, H Stenmark, A Simonsen, A Yamamoto; citation_volume=38; citation_publication_date=2010; citation_pages=265-279; citation_id=CR100"/> <meta name="citation_reference" content="citation_journal_title=Nat Immunol; citation_title=The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria; citation_author=TL Thurston, G Ryzhakov, S Bloor, N von Muhlinen, F Randow; citation_volume=10; citation_publication_date=2009; citation_pages=1215-1221; citation_id=CR101"/> <meta name="citation_reference" content="citation_journal_title=Science; citation_title=Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth; citation_author=P Wild, H Farhan, DG McEwan, S Wagner, VV Rogov, NR Brady, B Richter, J Korac, O Waidmann, C Choudhary, V Dötsch, D Bumann, I Dikic; citation_volume=333; citation_publication_date=2011; citation_pages=228-233; citation_id=CR102"/> <meta name="citation_reference" content="citation_journal_title=J Cell Sci; citation_title=The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes; citation_author=E Shvets, E Fass, R Scherz-Shouval, Z Elazar; citation_volume=121; citation_publication_date=2008; citation_pages=2685-2695; citation_id=CR103"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Structural basis for sorting mechanism of p62 in selective autophagy; citation_author=Y Ichimura, T Kumanomidou, YS Sou, T Mizushima, J Ezaki, T Ueno, E Kominami, T Yamane, K Tanaka, M Komatsu; citation_volume=283; citation_publication_date=2008; citation_pages=22847-22857; citation_id=CR104"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy; citation_author=S Pankiv, TH Clausen, T Lamark, A Brech, JA Bruun, H Outzen, A Overvatn, G Bjorkoy, T Johansen; citation_volume=282; citation_publication_date=2007; citation_pages=24131-24145; citation_id=CR105"/> <meta name="citation_reference" content="citation_journal_title=Nat Cell Biol; citation_title=Selective autophagy: ubiquitin-mediated recognition and beyond; citation_author=C Kraft, M Peter, K Hofmann; citation_volume=12; citation_publication_date=2010; citation_pages=836-841; citation_id=CR106"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3-Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway; citation_author=M Yamaguchi, NN Noda, H Nakatogawa, H Kumeta, Y Ohsumi, F Inagaki; citation_volume=285; citation_publication_date=2010; citation_pages=29599-29607; citation_id=CR107"/> <meta name="citation_reference" content="citation_journal_title=Genes Cells; citation_title=Structural basis of target recognition by Atg8/LC3 during selective autophagy; citation_author=NN Noda, H Kumeta, H Nakatogawa, K Satoo, W Adachi, J Ishii, Y Fujioka, Y Ohsumi, F Inagaki; citation_volume=13; citation_publication_date=2008; citation_pages=1211-1218; citation_id=CR108"/> <meta name="citation_reference" content="citation_journal_title=J Biol Chem; citation_title=Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism; citation_author=S Jiang, B Heller, VS Tagliabracci, L Zhai, JM Irimia, AA DePaoli-Roach, CD Wells, AV Skurat, PJ Roach; citation_volume=285; citation_publication_date=2010; citation_pages=34960-34971; citation_id=CR109"/> <meta name="citation_reference" content="citation_journal_title=Autophagy; citation_title=LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization; citation_author=A Kuma, M Matsui, N Mizushima; citation_volume=3; citation_publication_date=2007; citation_pages=323-328; citation_id=CR110"/> <meta name="citation_reference" content="citation_journal_title=Mol Biol Evol; citation_title=A phylogenomic investigation into the origin of metazoa; citation_author=I Ruiz-Trillo, AJ Roger, G Burger, MW Gray, BF Lang; citation_volume=25; citation_publication_date=2008; citation_pages=664-672; citation_id=CR111"/> <meta name="citation_reference" content="citation_journal_title=Dev Biol; citation_title=Meig1 deficiency causes a severe defect in mouse spermatogenesis; citation_author=Y Salzberg, T Eldar, OD Karminsky, SB Itach, S Pietrokovski, J Don; citation_volume=338; citation_publication_date=2010; citation_pages=158-167; citation_id=CR112"/> <meta name="citation_reference" content="citation_journal_title=Nucleic Acids Res; citation_title=Sequence logos: a new way to display consensus sequences; citation_author=TD Schneider, RM Stephens; citation_volume=18; citation_publication_date=1990; citation_pages=6097-6100; citation_id=CR113"/> <meta name="citation_reference" content="citation_journal_title=Nucleic Acids Res; citation_title=CDD: a Conserved Domain Database for the functional annotation of proteins; citation_author=A Marchler-Bauer, S Lu, JB Anderson, F Chitsaz, MK Derbyshire, C DeWeese-Scott, JH Fong, LY Geer, RC Geer, NR Gonzales, M Gwadz, DI Hurwitz, JD Jackson, Z Ke, CJ Lanczycki, F Lu, GH Marchler, M Mullokandov, MV Omelchenko, CL Robertson, JS Song, N Thanki, RA Yamashita, D Zhang, N Zhang, C Zheng, SH Bryant; citation_volume=39; citation_publication_date=2011; citation_pages=D225-D229; citation_id=CR114"/> <meta name="citation_reference" content="citation_journal_title=Nucleic Acids Res; citation_title=The Pfam protein families database; citation_author=RD Finn, J Mistry, J Tate, P Coggill, A Heger, JE Pollington, OL Gavin, P Gunasekaran, G Ceric, K Forslund, L Holm, EL Sonnhammer, SR Eddy, A Bateman; citation_volume=38; citation_publication_date=2010; citation_pages=D211-D222; citation_id=CR115"/> <meta name="citation_author" content="Shpilka, Tomer"/> <meta name="citation_author_institution" content="Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel"/> <meta name="citation_author" content="Weidberg, Hilla"/> <meta name="citation_author_institution" content="Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel"/> <meta name="citation_author" content="Pietrokovski, Shmuel"/> <meta name="citation_author_institution" content="Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel"/> <meta name="citation_author" content="Elazar, Zvulun"/> <meta name="citation_author_institution" content="Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel"/> <meta name="format-detection" content="telephone=no"> <link rel="apple-touch-icon" sizes="180x180" href=/static/img/favicons/bmc/apple-touch-icon-582ef1d0f5.png> <link rel="icon" type="image/png" sizes="192x192" href=/static/img/favicons/bmc/android-chrome-192x192-9625b7cdba.png> <link rel="icon" type="image/png" sizes="32x32" href=/static/img/favicons/bmc/favicon-32x32-5d7879efe1.png> <link rel="icon" type="image/png" sizes="16x16" href=/static/img/favicons/bmc/favicon-16x16-c241ac1a2f.png> <link rel="shortcut icon" data-test="shortcut-icon" href=/static/img/favicons/bmc/favicon-1886637b78.ico> <link rel="manifest" href=/static/app-bmc/manifest-3bb9ad383b.json> <meta name="msapplication-config" content=/static/app-bmc/browserconfig-ecd9aa8205.xml> <meta name="msapplication-TileColor" content="#1b3051"> <meta name="msapplication-TileImage" content=/static/img/favicons/bmc/app-icon-144x144.png> <meta name="theme-color" content="#1b3051"> <script>(function(H){H.className=H.className.replace(/\bno-js\b/,'js')})(document.documentElement)</script> <link rel="stylesheet" media="screen" href=/static/app-bmc/css/core-article-f3872e738d.css> <link rel="stylesheet" media="screen" href=/static/app-bmc/css/core-eac3097aa4.css> <link rel="stylesheet" media="print" href=/static/app-bmc/css/print-b8af42253b.css>  <style>@media only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark) { button{line-height:inherit}html,label{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}html{-webkit-font-smoothing:subpixel-antialiased;box-sizing:border-box;color:#333;font-size:100%;height:100%;line-height:1.61803;overflow-y:scroll}*{box-sizing:inherit}body{background:#fff;margin:0;max-width:100%;min-height:100%}button,div,form,input,p{margin:0;padding:0}body{padding:0}a{color:#004b83;text-decoration:underline;text-decoration-skip-ink:auto}a>img{vertical-align:middle}h1,h2{color:#1b3051;font-style:normal;font-weight:700}h1{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:28px;line-height:1.4}html.webfonts-loaded h1,html.webfonts-loaded h2,html.webfonts-loaded h3{font-family:Europa,Trebuchet MS}h2{font-size:26px;margin-bottom:.5em}h2,h3{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;line-height:1.4}h3{color:#1b3051;font-size:18px;font-style:normal;margin-bottom:.7em}.c-navbar{background:#f2f2f2;border-bottom:1px solid #d9d9d9;border-top:1px solid #d9d9d9;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:14px;line-height:1.61803;padding:16px 0}.c-navbar--with-submit-button{padding-bottom:24px}@media only screen and (min-width:540px){.c-navbar--with-submit-button{padding-bottom:16px}}.c-navbar__container{display:flex;flex-wrap:wrap;justify-content:space-between;margin:0 auto;max-width:1280px;padding:0 16px}.c-navbar__content{display:flex;flex:0 1 auto}.c-navbar__nav{align-items:center;display:flex;flex-wrap:wrap;gap:16px 16px;list-style:none;margin:0;padding:0}.c-navbar__item{flex:0 0 auto}.c-navbar__link{background:0 0;border:0;color:currentcolor;display:block;text-decoration:none;text-transform:capitalize}.c-navbar__link--is-shown{text-decoration:underline}.c-ad{text-align:center}@media only screen and (min-width:320px){.c-ad{padding:8px}}.c-ad--728x90{background-color:#ccc;display:none}.c-ad--728x90 .c-ad__inner{min-height:calc(1.5em + 94px)}.c-ad--728x90 iframe{height:90px;max-width:970px}@media only screen and (min-width:768px){.js .c-ad--728x90{display:none}.js .u-show-following-ad+.c-ad--728x90{display:block}}.c-ad iframe{border:0;overflow:auto;vertical-align:top}.c-ad__label{color:#333;font-weight:400;line-height:1.5;margin-bottom:4px}.c-ad__label,.c-skip-link{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:.875rem}.c-skip-link{background:#dceaf6;bottom:auto;color:#004b83;padding:8px;position:absolute;text-align:center;transform:translateY(-100%);z-index:9999}@media (prefers-reduced-motion:reduce){.c-skip-link{transition:top .3s ease-in-out 0s}}@media print{.c-skip-link{display:none}}.c-skip-link:link{color:#004b83}.c-dropdown__button:after{border-color:transparent transparent transparent #fff;border-style:solid;border-width:4px 0 4px 14px;content:"";display:block;height:0;margin-left:3px;width:0}.c-dropdown{display:inline-block;position:relative}.c-dropdown__button{background-color:transparent;border:0;display:inline-block;padding:0;white-space:nowrap}.c-dropdown__button:after{border-color:currentcolor transparent transparent;border-width:5px 4px 0 5px;display:inline-block;margin-left:8px;vertical-align:middle}.c-dropdown__menu{background-color:#fff;border:1px solid #d9d9d9;border-radius:3px;box-shadow:0 2px 6px rgba(0,0,0,.1);font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:14px;line-height:1.4;list-style:none;margin:0;padding:8px 0;position:absolute;top:100%;transform:translateY(8px);width:180px;z-index:100}.c-dropdown__menu:after,.c-dropdown__menu:before{border-style:solid;bottom:100%;content:"";display:block;height:0;left:16px;position:absolute;width:0}.c-dropdown__menu:before{border-color:transparent transparent #d9d9d9;border-width:0 9px 9px;transform:translateX(-1px)}.c-dropdown__menu:after{border-color:transparent transparent #fff;border-width:0 8px 8px}.c-dropdown__menu--right{left:auto;right:0}.c-dropdown__menu--right:after,.c-dropdown__menu--right:before{left:auto;right:16px}.c-dropdown__menu--right:before{transform:translateX(1px)}.c-dropdown__link{background-color:transparent;color:#004b83;display:block;padding:4px 16px}.c-header{background-color:#1b3051;border-bottom:4px solid #1b3051;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:14px;padding:16px 0}.c-header__container,.c-header__menu{align-items:center;display:flex;flex-wrap:wrap}@supports (gap:2em){.c-header__container,.c-header__menu{gap:2em 2em}}.c-header__menu{list-style:none;margin:0;padding:0}.c-header__item{color:#fff}@supports not (gap:2em){.c-header__item{margin-left:24px}}.c-header__container{justify-content:space-between;margin:0 auto;max-width:1280px;padding:0 16px}@supports not (gap:2em){.c-header__brand{margin-right:48px}}.c-header__brand a{display:block;text-decoration:none}.c-header__link{color:#fff}.c-journal-title a{text-decoration:none}html.webfonts-loaded .c-journal-title{font-family:Europa,Trebuchet MS}.c-form-field{margin-bottom:1em}.c-form-field__label{color:#666;display:block;font-size:14px;margin-bottom:.4em}.c-form-field__input{border:1px solid #a6a6a6;border-radius:3px;box-shadow:inset 0 1px 3px 0 rgba(0,0,0,.21);font-size:14px;line-height:1.28571;padding:.75em 1em;vertical-align:middle;width:100%}.c-popup-search{background-color:#25426f;box-shadow:0 3px 3px -3px rgba(0,0,0,.21);padding:16px 0;position:relative;z-index:10}@media only screen and (min-width:1024px){.js .c-popup-search{position:absolute;top:100%;width:100%}.c-popup-search__container{margin:auto;max-width:70%}}.c-logo img{display:block}.ctx-search .c-form-field{margin-bottom:0}.ctx-search .c-form-field__label{color:#fff}.ctx-search .c-form-field__input{border-bottom-right-radius:0;border-top-right-radius:0;margin-right:0}.c-journal-header{overflow:hidden}.c-journal-header__inner{padding-bottom:8px;padding-top:8px}@media only screen and (min-width:540px){.c-journal-header__inner{display:flex;justify-content:space-between}}.c-journal-header__identity{background-size:auto 80px;min-height:16px;padding:6px 0}@media only screen and (min-width:540px){.c-journal-header__identity{background-position:0}}.c-journal-header__identity--default{background:url(/static/images/bmc/identities/patterns/default-7e3a6b1388.svg) 0 0 no-repeat #04caa8}.c-journal-title{color:#1b3051;display:flex;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:26px;font-style:normal;font-weight:700;line-height:1.4;margin-bottom:0}.c-journal-title>a{color:#0061a9;color:#1b3051;display:flex;text-decoration:none}.c-journal-title__text{align-self:center;display:block;flex:0 1 auto}.c-logo,.c-logo>a{align-items:baseline;display:flex}.c-logo__strapline{display:none}@media only screen and (min-width:540px){.c-logo__strapline{display:block;margin:0 0 0 16px;transform:translateY(1px)}}.c-logo{display:block}html.webfonts-loaded .u-h3,html.webfonts-loaded .u-h4{font-family:Europa,Trebuchet MS}.u-button{align-items:center;background-color:#f2f2f2;background-image:linear-gradient(#fff,#f2f2f2);border:1px solid #ccc;border-radius:2px;cursor:pointer;display:inline-flex;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1rem;justify-content:center;line-height:1.3;margin:0;padding:8px;position:relative;text-decoration:none;transition:all .25s ease 0s,color .25s ease 0s,border-color .25s ease 0s;width:auto}.u-button svg,.u-button--primary svg,.u-button--tertiary svg{fill:currentcolor}.u-button{color:#004b83}.u-button--primary,.u-button--tertiary{background-color:#33629d;background-image:linear-gradient(#4d76a9,#33629d);border:1px solid rgba(0,59,132,.5);color:#fff}.u-button--tertiary{font-weight:400}.u-button--full-width{display:flex;width:100%}.u-clearfix:after,.u-clearfix:before{content:"";display:table}.u-clearfix:after{clear:both}.u-color-open-access{color:#b74616}.u-container{margin:0 auto;max-width:1280px;padding:0 16px}.u-display-flex{display:flex;width:100%}.u-align-items-center{align-items:center}.u-justify-content-space-between{justify-content:space-between}.u-flex-static{flex:0 0 auto}.u-display-none{display:none}.js .u-js-hide{display:none;visibility:hidden}@media print{.u-hide-print{display:none}}.u-icon{fill:currentcolor;display:inline-block;height:1em;transform:translate(0);vertical-align:text-top;width:1em}.u-list-reset{list-style:none;margin:0;padding:0}.u-position-relative{position:relative}.u-mt-32{margin-top:32px}.u-mr-24{margin-right:24px}.u-mr-48{margin-right:48px}.u-mb-32{margin-bottom:32px}.u-ml-8{margin-left:8px}.u-button-reset{background-color:transparent;border:0;padding:0}.u-text-sm{font-size:14px}.u-h3,.u-h4{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;line-height:1.4}.u-h3{color:#1b3051;font-size:18px;font-style:normal;margin-bottom:.7em}.u-h4{color:#1b3051;font-size:18px;font-style:italic;font-weight:700;margin-bottom:.7em}.u-vh-full{min-height:100vh}.u-hide{display:none;visibility:hidden}.u-hide:first-child+*{margin-block-start:0}@media only screen and (min-width:1024px){.u-hide-at-lg{display:none;visibility:hidden}}@media only screen and (max-width:1023px){.u-hide-at-lt-lg{display:none;visibility:hidden}.u-hide-at-lt-lg:first-child+*{margin-block-start:0}}.u-visually-hidden{clip:rect(0,0,0,0);border:0;height:1px;margin:-100%;overflow:hidden;padding:0;position:absolute!important;width:1px}.u-button--tertiary{font-size:.875rem;padding:8px 16px}@media only screen and (max-width:539px){.u-button--alt-colour-on-mobile{background-color:#f2f2f2;background-image:linear-gradient(#fff,#f2f2f2);border:1px solid #ccc;color:#004b83}}body{font-size:1.125rem}.c-header__navigation{display:flex;gap:.5rem .5rem} }</style> <style>@media only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark) { button{line-height:inherit}html,label{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}html{-webkit-font-smoothing:subpixel-antialiased;box-sizing:border-box;color:#333;font-size:100%;height:100%;line-height:1.61803;overflow-y:scroll}*{box-sizing:inherit}body{background:#fff;margin:0;max-width:100%;min-height:100%}button,div,form,input,p{margin:0;padding:0}body{padding:0}a{color:#004b83;overflow-wrap:break-word;text-decoration:underline;text-decoration-skip-ink:auto;word-break:break-word}a>img{vertical-align:middle}h1,h2{color:#1b3051;font-style:normal;font-weight:700}h1{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:28px;line-height:1.4}html.webfonts-loaded h1,html.webfonts-loaded h2,html.webfonts-loaded h3{font-family:Europa,Trebuchet MS}h2{font-size:26px;margin-bottom:.5em}h2,h3{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;line-height:1.4}h3{color:#1b3051;font-size:18px;font-style:normal;margin-bottom:.7em}p{overflow-wrap:break-word;word-break:break-word}.u-h3{font-size:1.5rem}.u-h3,.u-h4{font-weight:700}.u-h4{font-size:1.25rem}.c-reading-companion__figure-title{font-size:1.25rem;font-weight:700}body{font-size:1.125rem}.c-article-header{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;margin-bottom:40px}.c-article-identifiers{color:#6f6f6f;display:flex;flex-wrap:wrap;font-size:1rem;line-height:1.3;list-style:none;margin:0 0 8px;padding:0}.c-article-identifiers__item{border-right:1px solid #6f6f6f;list-style:none;margin-right:8px;padding-right:8px}.c-article-identifiers__item:last-child{border-right:0;margin-right:0;padding-right:0}.c-article-title{font-size:1.5rem;line-height:1.25;margin-bottom:16px}@media only screen and (min-width:768px){.c-article-title{font-size:1.875rem;line-height:1.2}}.c-article-author-list{display:inline;font-size:1rem;list-style:none;margin:0 8px 0 0;padding:0;width:100%}.c-article-author-list__item{display:inline;padding-right:0}.c-article-author-list svg{margin-left:4px}.c-article-author-list__show-more{display:none;margin-right:4px}.c-article-author-list__button,.js .c-article-author-list__item--hide,.js .c-article-author-list__show-more{display:none}.js .c-article-author-list--long .c-article-author-list__show-more,.js .c-article-author-list--long+.c-article-author-list__button{display:inline}@media only screen and (max-width:539px){.js .c-article-author-list__item--hide-small-screen{display:none}.js .c-article-author-list--short .c-article-author-list__show-more,.js .c-article-author-list--short+.c-article-author-list__button{display:inline}}#uptodate-client,.js .c-article-author-list--expanded .c-article-author-list__show-more{display:none!important}.js .c-article-author-list--expanded .c-article-author-list__item--hide-small-screen{display:inline!important}.c-article-author-list__button,.c-button-author-list{background:#ebf1f5;border:4px solid #ebf1f5;border-radius:20px;color:#666;font-size:.875rem;line-height:1.4;padding:2px 11px 2px 8px;text-decoration:none}.c-article-author-list__button svg,.c-button-author-list svg{margin:1px 4px 0 0}.c-article-author-list__button:hover,.c-button-author-list:hover{background:#173962;border-color:transparent;color:#fff}.c-article-info-details{font-size:1rem;margin-bottom:8px;margin-top:16px}.c-article-info-details__cite-as{border-left:1px solid #6f6f6f;margin-left:8px;padding-left:8px}.c-article-metrics-bar{display:flex;flex-wrap:wrap;font-size:1rem;line-height:1.3}.c-article-metrics-bar__wrapper{margin:0 0 16px}.c-article-metrics-bar__item{align-items:baseline;border-right:1px solid #6f6f6f;margin-right:8px}.c-article-metrics-bar__item:last-child{border-right:0}.c-article-metrics-bar__count{font-weight:700;margin:0}.c-article-metrics-bar__label{color:#626262;font-style:normal;font-weight:400;margin:0 10px 0 5px}.c-article-metrics-bar__details{margin:0}.c-article-main-column{font-family:Georgia,Palatino,serif;margin-right:8.6%;width:60.2%}@media only screen and (max-width:1023px){.c-article-main-column{margin-right:0;width:100%}}.c-article-extras{float:left;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;width:31.2%}@media only screen and (max-width:1023px){.c-article-extras{display:none}}.c-article-associated-content__container .c-article-associated-content__title,.c-article-section__title{border-bottom:2px solid #d5d5d5;font-size:1.25rem;margin:0;padding-bottom:8px}@media only screen and (min-width:768px){.c-article-associated-content__container .c-article-associated-content__title,.c-article-section__title{font-size:1.5rem;line-height:1.24}}.c-article-associated-content__container .c-article-associated-content__title{margin-bottom:8px}.c-article-section{clear:both}.c-article-section__content{margin-bottom:40px;margin-top:0;padding-top:8px}@media only screen and (max-width:1023px){.c-article-section__content{padding-left:0}}.c-article__sub-heading{color:#222;font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif;font-size:1.125rem;font-style:normal;font-weight:400;line-height:1.3;margin:24px 0 8px}@media only screen and (min-width:768px){.c-article__sub-heading{font-size:1.5rem;line-height:1.24}}.c-article__sub-heading:first-child{margin-top:0}.c-article-authors-search{margin-bottom:24px;margin-top:0}.c-article-authors-search__item,.c-article-authors-search__title{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif}.c-article-authors-search__title{color:#626262;font-size:1.05rem;font-weight:700;margin:0;padding:0}.c-article-authors-search__item{font-size:1rem}.c-article-authors-search__text{margin:0}.c-article-share-box__no-sharelink-info{font-size:.813rem;font-weight:700;margin-bottom:24px;padding-top:4px}.c-article-share-box__only-read-input{border:1px solid #d5d5d5;box-sizing:content-box;display:inline-block;font-size:.875rem;font-weight:700;height:24px;margin-bottom:8px;padding:8px 10px}.c-article-share-box__button--link-like{background-color:transparent;border:0;color:#0067c5;cursor:pointer;font-size:.875rem;margin-bottom:8px;margin-left:10px}.c-article-associated-content__container .c-article-associated-content__collection-label{font-size:.875rem;line-height:1.4}.c-article-associated-content__container .c-article-associated-content__collection-title{line-height:1.3}.c-context-bar{box-shadow:0 0 10px 0 rgba(51,51,51,.2);position:relative;width:100%}.c-context-bar__title{display:none}.c-reading-companion{clear:both;min-height:389px}.c-reading-companion__sticky{max-width:389px}.c-reading-companion__scroll-pane{margin:0;min-height:200px;overflow:hidden auto}.c-reading-companion__tabs{display:flex;flex-flow:row nowrap;font-size:1rem;list-style:none;margin:0 0 8px;padding:0}.c-reading-companion__tabs>li{flex-grow:1}.c-reading-companion__tab{background-color:#eee;border:1px solid #d5d5d5;border-image:initial;border-left-width:0;color:#0067c5;font-size:1rem;padding:8px 8px 8px 15px;text-align:left;width:100%}.c-reading-companion__tabs li:first-child .c-reading-companion__tab{border-left-width:1px}.c-reading-companion__tab--active{background-color:#fff;border-bottom:1px solid #fff;color:#222;font-weight:700}.c-reading-companion__sections-list{list-style:none;padding:0}.c-reading-companion__figures-list,.c-reading-companion__references-list{list-style:none;min-height:389px;padding:0}.c-reading-companion__references-list--numeric{list-style:decimal inside}.c-reading-companion__sections-list{margin:0 0 8px;min-height:50px}.c-reading-companion__section-item{font-size:1rem;padding:0}.c-reading-companion__section-item a{display:block;line-height:1.5;overflow:hidden;padding:8px 0 8px 16px;text-overflow:ellipsis;white-space:nowrap}.c-reading-companion__figure-item{border-top:1px solid #d5d5d5;font-size:1rem;padding:16px 8px 16px 0}.c-reading-companion__figure-item:first-child{border-top:none;padding-top:8px}.c-reading-companion__reference-item{border-top:1px solid #d5d5d5;font-size:1rem;padding:8px 8px 8px 16px}.c-reading-companion__reference-item:first-child{border-top:none}.c-reading-companion__reference-item a{word-break:break-word}.c-reading-companion__reference-citation{display:inline}.c-reading-companion__reference-links{font-size:.813rem;font-weight:700;list-style:none;margin:8px 0 0;padding:0;text-align:right}.c-reading-companion__reference-links>a{display:inline-block;padding-left:8px}.c-reading-companion__reference-links>a:first-child{display:inline-block;padding-left:0}.c-reading-companion__figure-title{display:block;margin:0 0 8px}.c-reading-companion__figure-links{display:flex;justify-content:space-between;margin:8px 0 0}.c-reading-companion__figure-links>a{align-items:center;display:flex}.c-reading-companion__figure-full-link svg{height:.8em;margin-left:2px}.c-reading-companion__panel{border-top:none;display:none;margin-top:0;padding-top:0}.c-reading-companion__panel--active{display:block}.c-pdf-download__link .u-icon{padding-top:2px}.c-pdf-download{display:flex;margin-bottom:16px;max-height:48px}@media only screen and (min-width:540px){.c-pdf-download{max-height:none}}@media only screen and (min-width:1024px){.c-pdf-download{max-height:48px}}.c-pdf-download__link{display:flex;flex:1 1 0%;padding:13px 24px!important}.c-pdf-download__text{padding-right:4px}@media only screen and (max-width:539px){.c-pdf-download__text{text-transform:capitalize}}@media only screen and (min-width:540px){.c-pdf-download__text{padding-right:8px}}.c-pdf-container{display:flex;justify-content:flex-end}@media only screen and (max-width:539px){.c-pdf-container .c-pdf-download{display:flex;flex-basis:100%}}.c-article-associated-content__container a,.c-card__summary a{text-decoration:underline}.u-display-none{display:none}.js .u-js-hide,.u-hide{display:none;visibility:hidden}.u-hide:first-child+*{margin-block-start:0}.u-visually-hidden{clip:rect(0,0,0,0);border:0;height:1px;margin:-100%;overflow:hidden;padding:0;position:absolute!important;width:1px}@media print{.u-hide-print{display:none}}@media only screen and (min-width:1024px){.u-hide-at-lg{display:none;visibility:hidden}}.u-icon{fill:currentcolor;display:inline-block;height:1em;transform:translate(0);vertical-align:text-top;width:1em}.u-list-reset{list-style:none;margin:0;padding:0}.hide{display:none;visibility:hidden}.c-article-associated-content__container .c-article-associated-content__collection.collection~.c-article-associated-content__collection.collection .c-article-associated-content__collection-label,.c-article-associated-content__container .c-article-associated-content__collection.section~.c-article-associated-content__collection.section .c-article-associated-content__collection-label,.c-article-associated-content__container .c-article-associated-content__title{display:none}.c-article-associated-content__container .c-article-associated-content__collection.collection .c-article-associated-content__collection-label,.c-article-associated-content__container .c-article-associated-content__collection.section .c-article-associated-content__collection-label{display:block}.c-article-associated-content__container .c-article-associated-content__collection.collection,.c-article-associated-content__container .c-article-associated-content__collection.section{margin-bottom:5px}.c-article-associated-content__container .c-article-associated-content__collection.section~.c-article-associated-content__collection.collection{margin-top:28px}.c-article-associated-content__container .c-article-associated-content__collection:first-child{margin-top:0}.c-article-associated-content__container .c-article-associated-content__collection:last-child{margin-bottom:2.4rem}.c-article-associated-content__container .c-article-associated-content__collection-label{color:#1b3051}.c-article-associated-content__container .c-article-associated-content__collection-title{font-size:1.063rem;font-weight:400}.webfonts-loaded .c-article__sub-heading{font-family:-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Oxygen-Sans,Ubuntu,Cantarell,Helvetica Neue,sans-serif} }</style> <link rel="stylesheet" data-test="critical-css-handler" data-inline-css-source="critical-css" href="/static/app-bmc/css/enhanced-32c9abc865.css" media="print" onload="this.media='only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)';this.onload=null"> <link rel="stylesheet" data-test="critical-css-handler" data-inline-css-source="critical-css" href="/static/app-bmc/css/enhanced-article-215af16b37.css" media="print" onload="this.media='only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)';this.onload=null"> <script type="text/javascript"> config = { env: 'live', site: 'genomebiology.biomedcentral.com', siteWithPath: 'genomebiology.biomedcentral.com' + window.location.pathname, twitterHashtag: '', cmsPrefix: 'https://studio-cms.springernature.com/studio/', doi: '10.1186/gb-2011-12-7-226', figshareScriptUrl: 'https://widgets.figshare.com/static/figshare.js', hasFigshareInvoked: false, publisherBrand: 'BioMed Central', mustardcut: false }; </script> <script type="text/javascript" data-test="dataLayer"> window.dataLayer = [{"content":{"article":{"doi":"10.1186/gb-2011-12-7-226","articleType":"Protein family review","peerReviewType":"Closed","supplement":null,"keywords":"Autophagosome Formation;Autophagic Process;Atg8 Gene;Multicellular Animal;Atg8 Protein"},"contentInfo":{"imprint":"BioMed Central","title":"Atg8: an autophagy-related ubiquitin-like protein family","publishedAt":1311724800000,"publishedAtDate":"2011-07-27","author":["Tomer Shpilka","Hilla Weidberg","Shmuel Pietrokovski","Zvulun Elazar"],"collection":[]},"attributes":{"deliveryPlatform":"oscar","template":"rebrand","cms":null,"copyright":{"creativeCommonsType":null,"openAccess":false},"environment":"live"},"journal":{"siteKey":"genomebiology.biomedcentral.com","volume":"12","issue":"7","title":"Genome Biology","type":"FLAGSHIP","journalID":13059,"section":[]},"category":{"pmc":{"primarySubject":"Life Sciences"},"contentType":"Protein family review","publishingSegment":"BMC Flagships","snt":["Genetics and Genomics","Epigenetics","Bioinformatics","Plant Genetics","Microbial Genetics","Evolutionary Biology"]}},"session":{"authentication":{"authenticationID":[]}},"version":"1.0.0","page":{"category":{"pageType":"article"},"attributes":{"featureFlags":[],"environment":"live","darwin":false}},"japan":false,"event":"dataLayerCreated","collection":null,"publisherBrand":"BioMed Central"}]; </script> <script> window.dataLayer = window.dataLayer || []; window.dataLayer.push({ ga4MeasurementId: 'G-PJCTJWPV25', ga360TrackingId: 'UA-54492316-9', twitterId: 'o47a2', baiduId: 'd1b4bc3b5ada4eb7290535e72899bac1', ga4ServerUrl: 'https://collect.biomedcentral.com', imprint: 'biomedcentral' }); </script> <script> (function(w, d) { w.config = w.config || {}; w.config.mustardcut = false; if (w.matchMedia && w.matchMedia('only print, only all and (prefers-color-scheme: no-preference), only all and (prefers-color-scheme: light), only all and (prefers-color-scheme: dark)').matches) { w.config.mustardcut = true; d.classList.add('js'); d.classList.remove('grade-c'); d.classList.remove('no-js'); } })(window, document.documentElement); </script> <script> (function () { if ( typeof window.CustomEvent === "function" ) return false; function CustomEvent ( event, params ) { params = params || { bubbles: false, cancelable: false, detail: null }; var evt = document.createEvent( 'CustomEvent' ); evt.initCustomEvent( event, params.bubbles, params.cancelable, params.detail ); return evt; } CustomEvent.prototype = window.Event.prototype; window.CustomEvent = CustomEvent; })(); </script> <script class="js-entry"> if (window.config.mustardcut) { (function(w, d) { window.Component = {}; window.suppressShareButton = true; window.onArticlePage = true; var currentScript = d.currentScript || d.head.querySelector('script.js-entry'); function catchNoModuleSupport() { var scriptEl = d.createElement('script'); return (!('noModule' in scriptEl) && 'onbeforeload' in scriptEl) } var headScripts = [ {'src': '/static/js/polyfill-es5-bundle-572d4fec60.js', 'async': false} ]; var bodyScripts = [ {'src': '/static/js/app-es5-bundle-d0ac94c97e.js', 'async': false, 'module': false}, {'src': '/static/js/app-es6-bundle-5ee1a6879c.js', 'async': false, 'module': true} , {'src': '/static/js/global-article-es5-bundle-ae3b685a1c.js', 'async': false, 'module': false}, {'src': '/static/js/global-article-es6-bundle-f72e3cd2ca.js', 'async': false, 'module': true} ]; function createScript(script) { var scriptEl = d.createElement('script'); scriptEl.src = script.src; scriptEl.async = script.async; if (script.module === true) { scriptEl.type = "module"; if (catchNoModuleSupport()) { scriptEl.src = ''; } } else if (script.module === false) { scriptEl.setAttribute('nomodule', true) } if (script.charset) { scriptEl.setAttribute('charset', script.charset); } return scriptEl; } for (var i = 0; i < headScripts.length; ++i) { var scriptEl = createScript(headScripts[i]); currentScript.parentNode.insertBefore(scriptEl, currentScript.nextSibling); } d.addEventListener('DOMContentLoaded', function() { for (var i = 0; i < bodyScripts.length; ++i) { var scriptEl = createScript(bodyScripts[i]); d.body.appendChild(scriptEl); } }); // Webfont repeat view var config = w.config; if (config && config.publisherBrand && sessionStorage.fontsLoaded === 'true') { d.documentElement.className += ' webfonts-loaded'; } })(window, document); } </script> <script data-src="https://cdn.optimizely.com/js/27195530232.js" data-cc-script="C03"></script> <script data-test="gtm-head"> window.initGTM = function() { (function (w, d, s, l, i) { w[l] = w[l] || []; w[l].push({'gtm.start': new Date().getTime(), event: 'gtm.js'}); var f = d.getElementsByTagName(s)[0], j = d.createElement(s), dl = l != 'dataLayer' ? '&l=' + l : ''; j.async = true; j.src = 'https://www.googletagmanager.com/gtm.js?id=' + i + dl; f.parentNode.insertBefore(j, f); })(window, document, 'script', 'dataLayer', 'GTM-MRVXSHQ'); } </script> <meta name="360-site-verification" content="2e1d87196f82c9ac5454a21aede69eda" /> <script> (function (w, d, t) { function cc() { var h = w.location.hostname; var e = d.createElement(t), s = d.getElementsByTagName(t)[0]; if (h.indexOf('springer.com') > -1 && h.indexOf('biomedcentral.com') === -1 && h.indexOf('springeropen.com') === -1) { if (h.indexOf('link-qa.springer.com') > -1 || h.indexOf('test-www.springer.com') > -1) { e.src = 'https://cmp.springer.com/production_live/en/consent-bundle-17-52.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } else { e.src = 'https://cmp.springer.com/production_live/en/consent-bundle-17-52.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } } else if (h.indexOf('biomedcentral.com') > -1) { if (h.indexOf('biomedcentral.com.qa') > -1) { e.src = 'https://cmp.biomedcentral.com/production_live/en/consent-bundle-15-36.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } else { e.src = 'https://cmp.biomedcentral.com/production_live/en/consent-bundle-15-36.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } } else if (h.indexOf('springeropen.com') > -1) { if (h.indexOf('springeropen.com.qa') > -1) { e.src = 'https://cmp.springernature.com/production_live/en/consent-bundle-16-34.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } else { e.src = 'https://cmp.springernature.com/production_live/en/consent-bundle-16-34.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-MRVXSHQ')"); } } else if (h.indexOf('springernature.com') > -1) { if (h.indexOf('beta-qa.springernature.com') > -1) { e.src = 'https://cmp.springernature.com/production_live/en/consent-bundle-49-43.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-NK22KLS')"); } else { e.src = 'https://cmp.springernature.com/production_live/en/consent-bundle-49-43.js'; e.setAttribute('onload', "initGTM(window,document,'script','dataLayer','GTM-NK22KLS')"); } } else { e.src = '/static/js/cookie-consent-es5-bundle-cb57c2c98a.js'; e.setAttribute('data-consent', h); } s.insertAdjacentElement('afterend', e); } cc(); })(window, document, 'script'); </script> <link rel="canonical" href="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-7-226"/> <meta property="og:url" content="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-7-226"/> <meta property="og:type" content="article"/> <meta property="og:site_name" content="BioMed Central"/> <meta property="og:title" content="Atg8: an autophagy-related ubiquitin-like protein family - Genome Biology"/> <meta property="og:description" content="Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective."/> <meta property="og:image" content="https://static-content.springer.com/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig1_HTML.jpg"/> <script type="application/ld+json">{"mainEntity":{"headline":"Atg8: an autophagy-related ubiquitin-like protein family","description":"Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective.","datePublished":"2011-07-27T00:00:00Z","dateModified":"2011-07-27T00:00:00Z","pageStart":"1","pageEnd":"11","sameAs":"https://doi.org/10.1186/gb-2011-12-7-226","keywords":["Autophagosome Formation","Autophagic Process","Atg8 Gene","Multicellular Animal","Atg8 Protein","Animal Genetics and Genomics","Human Genetics","Plant Genetics and Genomics","Microbial Genetics and Genomics","Bioinformatics","Evolutionary Biology"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig1_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig2_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig3_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig4_HTML.jpg"],"isPartOf":{"name":"Genome Biology","issn":["1474-760X"],"volumeNumber":"12","@type":["Periodical","PublicationVolume"]},"publisher":{"name":"BioMed Central","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"Tomer Shpilka","affiliation":[{"name":"The Weizmann Institute of Science","address":{"name":"Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Hilla Weidberg","affiliation":[{"name":"The Weizmann Institute of Science","address":{"name":"Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"},{"name":"Shmuel Pietrokovski","affiliation":[{"name":"The Weizmann Institute of Science","address":{"name":"Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel","@type":"PostalAddress"},"@type":"Organization"}],"email":"shmuel.pietrokovski@weizmann.ac.il","@type":"Person"},{"name":"Zvulun Elazar","affiliation":[{"name":"The Weizmann Institute of Science","address":{"name":"Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel","@type":"PostalAddress"},"@type":"Organization"}],"email":"zvulun.elazar@weizmann.ac.il","@type":"Person"}],"isAccessibleForFree":true,"@type":"ScholarlyArticle"},"@context":"https://schema.org","@type":"WebPage"}</script> </head> <body class="journal journal-fulltext" > <div class="ctm"></div>  <noscript> <iframe src="https://www.googletagmanager.com/ns.html?id=GTM-MRVXSHQ" height="0" width="0" style="display:none;visibility:hidden"></iframe> </noscript>  <div class="u-visually-hidden" aria-hidden="true"> <?xml version="1.0" encoding="UTF-8"?><!DOCTYPE svg PUBLIC "-//W3C//DTD SVG 1.1//EN" "http://www.w3.org/Graphics/SVG/1.1/DTD/svg11.dtd"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><defs><path id="a" d="M0 .74h56.72v55.24H0z"/></defs><symbol id="icon-access" viewBox="0 0 18 18"><path d="m14 8c.5522847 0 1 .44771525 1 1v7h2.5c.2761424 0 .5.2238576.5.5v1.5h-18v-1.5c0-.2761424.22385763-.5.5-.5h2.5v-7c0-.55228475.44771525-1 1-1s1 .44771525 1 1v6.9996556h8v-6.9996556c0-.55228475.4477153-1 1-1zm-8 0 2 1v5l-2 1zm6 0v7l-2-1v-5zm-2.42653766-7.59857636 7.03554716 4.92488299c.4162533.29137735.5174853.86502537.226108 1.28127873-.1721584.24594054-.4534847.39241464-.7536934.39241464h-14.16284822c-.50810197 0-.92-.41189803-.92-.92 0-.30020869.1464741-.58153499.39241464-.75369337l7.03554714-4.92488299c.34432015-.2410241.80260453-.2410241 1.14692468 0zm-.57346234 2.03988748-3.65526982 2.55868888h7.31053962z" fill-rule="evenodd"/></symbol><symbol id="icon-account" viewBox="0 0 18 18"><path d="m10.2379028 16.9048051c1.3083556-.2032362 2.5118471-.7235183 3.5294683-1.4798399-.8731327-2.5141501-2.0638925-3.935978-3.7673711-4.3188248v-1.27684611c1.1651924-.41183641 2-1.52307546 2-2.82929429 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.30621883.83480763 2.41745788 2 2.82929429v1.27684611c-1.70347856.3828468-2.89423845 1.8046747-3.76737114 4.3188248 1.01762123.7563216 2.22111275 1.2766037 3.52946833 1.4798399.40563808.0629726.81921174.0951949 1.23790281.0951949s.83226473-.0322223 1.2379028-.0951949zm4.3421782-2.1721994c1.4927655-1.4532925 2.419919-3.484675 2.419919-5.7326057 0-4.418278-3.581722-8-8-8s-8 3.581722-8 8c0 2.2479307.92715352 4.2793132 2.41991895 5.7326057.75688473-2.0164459 1.83949951-3.6071894 3.48926591-4.3218837-1.14534283-.70360829-1.90918486-1.96796271-1.90918486-3.410722 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.44275929-.763842 2.70711371-1.9091849 3.410722 1.6497664.7146943 2.7323812 2.3054378 3.4892659 4.3218837zm-5.580081 3.2673943c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-alert" viewBox="0 0 18 18"><path d="m4 10h2.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-3.08578644l-1.12132034 1.1213203c-.18753638.1875364-.29289322.4418903-.29289322.7071068v.1715729h14v-.1715729c0-.2652165-.1053568-.5195704-.2928932-.7071068l-1.7071068-1.7071067v-3.4142136c0-2.76142375-2.2385763-5-5-5-2.76142375 0-5 2.23857625-5 5zm3 4c0 1.1045695.8954305 2 2 2s2-.8954305 2-2zm-5 0c-.55228475 0-1-.4477153-1-1v-.1715729c0-.530433.21071368-1.0391408.58578644-1.4142135l1.41421356-1.4142136v-3c0-3.3137085 2.6862915-6 6-6s6 2.6862915 6 6v3l1.4142136 1.4142136c.3750727.3750727.5857864.8837805.5857864 1.4142135v.1715729c0 .5522847-.4477153 1-1 1h-4c0 1.6568542-1.3431458 3-3 3-1.65685425 0-3-1.3431458-3-3z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-broad" viewBox="0 0 16 16"><path d="m6.10307866 2.97190702v7.69043288l2.44965196-2.44676915c.38776071-.38730439 1.0088052-.39493524 1.38498697-.01919617.38609051.38563612.38643641 1.01053024-.00013864 1.39665039l-4.12239817 4.11754683c-.38616704.3857126-1.01187344.3861062-1.39846576-.0000311l-4.12258206-4.11773056c-.38618426-.38572979-.39254614-1.00476697-.01636437-1.38050605.38609047-.38563611 1.01018509-.38751562 1.4012233.00306241l2.44985644 2.4469734v-8.67638639c0-.54139983.43698413-.98042709.98493125-.98159081l7.89910522-.0043627c.5451687 0 .9871152.44142642.9871152.98595351s-.4419465.98595351-.9871152.98595351z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 14 15)"/></symbol><symbol id="icon-arrow-down" viewBox="0 0 16 16"><path d="m3.28337502 11.5302405 4.03074001 4.176208c.37758093.3912076.98937525.3916069 1.367372-.0000316l4.03091977-4.1763942c.3775978-.3912252.3838182-1.0190815.0160006-1.4001736-.3775061-.39113013-.9877245-.39303641-1.3700683.003106l-2.39538585 2.4818345v-11.6147896l-.00649339-.11662112c-.055753-.49733869-.46370161-.88337888-.95867408-.88337888-.49497246 0-.90292107.38604019-.95867408.88337888l-.00649338.11662112v11.6147896l-2.39518594-2.4816273c-.37913917-.39282218-.98637524-.40056175-1.35419292-.0194697-.37750607.3911302-.37784433 1.0249269.00013556 1.4165479z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-left" viewBox="0 0 16 16"><path d="m4.46975946 3.28337502-4.17620792 4.03074001c-.39120768.37758093-.39160691.98937525.0000316 1.367372l4.1763942 4.03091977c.39122514.3775978 1.01908149.3838182 1.40017357.0160006.39113012-.3775061.3930364-.9877245-.00310603-1.3700683l-2.48183446-2.39538585h11.61478958l.1166211-.00649339c.4973387-.055753.8833789-.46370161.8833789-.95867408 0-.49497246-.3860402-.90292107-.8833789-.95867408l-.1166211-.00649338h-11.61478958l2.4816273-2.39518594c.39282216-.37913917.40056173-.98637524.01946965-1.35419292-.39113012-.37750607-1.02492687-.37784433-1.41654791.00013556z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-right" viewBox="0 0 16 16"><path d="m11.5302405 12.716625 4.176208-4.03074003c.3912076-.37758093.3916069-.98937525-.0000316-1.367372l-4.1763942-4.03091981c-.3912252-.37759778-1.0190815-.38381821-1.4001736-.01600053-.39113013.37750607-.39303641.98772445.003106 1.37006824l2.4818345 2.39538588h-11.6147896l-.11662112.00649339c-.49733869.055753-.88337888.46370161-.88337888.95867408 0 .49497246.38604019.90292107.88337888.95867408l.11662112.00649338h11.6147896l-2.4816273 2.39518592c-.39282218.3791392-.40056175.9863753-.0194697 1.3541929.3911302.3775061 1.0249269.3778444 1.4165479-.0001355z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-sub" viewBox="0 0 16 16"><path d="m7.89692134 4.97190702v7.69043288l-2.44965196-2.4467692c-.38776071-.38730434-1.0088052-.39493519-1.38498697-.0191961-.38609047.3856361-.38643643 1.0105302.00013864 1.3966504l4.12239817 4.1175468c.38616704.3857126 1.01187344.3861062 1.39846576-.0000311l4.12258202-4.1177306c.3861843-.3857298.3925462-1.0047669.0163644-1.380506-.3860905-.38563612-1.0101851-.38751563-1.4012233.0030624l-2.44985643 2.4469734v-8.67638639c0-.54139983-.43698413-.98042709-.98493125-.98159081l-7.89910525-.0043627c-.54516866 0-.98711517.44142642-.98711517.98595351s.44194651.98595351.98711517.98595351z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-up" viewBox="0 0 16 16"><path d="m12.716625 4.46975946-4.03074003-4.17620792c-.37758093-.39120768-.98937525-.39160691-1.367372.0000316l-4.03091981 4.1763942c-.37759778.39122514-.38381821 1.01908149-.01600053 1.40017357.37750607.39113012.98772445.3930364 1.37006824-.00310603l2.39538588-2.48183446v11.61478958l.00649339.1166211c.055753.4973387.46370161.8833789.95867408.8833789.49497246 0 .90292107-.3860402.95867408-.8833789l.00649338-.1166211v-11.61478958l2.39518592 2.4816273c.3791392.39282216.9863753.40056173 1.3541929.01946965.3775061-.39113012.3778444-1.02492687-.0001355-1.41654791z" fill-rule="evenodd"/></symbol><symbol id="icon-article" viewBox="0 0 18 18"><path d="m13 15v-12.9906311c0-.0073595-.0019884-.0093689.0014977-.0093689l-11.00158888.00087166v13.00506804c0 .5482678.44615281.9940603.99415146.9940603h10.27350412c-.1701701-.2941734-.2675644-.6357129-.2675644-1zm-12 .0059397v-13.00506804c0-.5562408.44704472-1.00087166.99850233-1.00087166h11.00299537c.5510129 0 .9985023.45190985.9985023 1.0093689v2.9906311h3v9.9914698c0 1.1065798-.8927712 2.0085302-1.9940603 2.0085302h-12.01187942c-1.09954652 0-1.99406028-.8927712-1.99406028-1.9940603zm13-9.0059397v9c0 .5522847.4477153 1 1 1s1-.4477153 1-1v-9zm-10-2h7v4h-7zm1 1v2h5v-2zm-1 4h7v1h-7zm0 2h7v1h-7zm0 2h7v1h-7z" fill-rule="evenodd"/></symbol><symbol id="icon-audio" viewBox="0 0 18 18"><path d="m13.0957477 13.5588459c-.195279.1937043-.5119137.193729-.7072234.0000551-.1953098-.193674-.1953346-.5077061-.0000556-.7014104 1.0251004-1.0168342 1.6108711-2.3905226 1.6108711-3.85745208 0-1.46604976-.5850634-2.83898246-1.6090736-3.85566829-.1951894-.19379323-.1950192-.50782531.0003802-.70141028.1953993-.19358497.512034-.19341614.7072234.00037709 1.2094886 1.20083761 1.901635 2.8250555 1.901635 4.55670148 0 1.73268608-.6929822 3.35779608-1.9037571 4.55880738zm2.1233994 2.1025159c-.195234.193749-.5118687.1938462-.7072235.0002171-.1953548-.1936292-.1954528-.5076613-.0002189-.7014104 1.5832215-1.5711805 2.4881302-3.6939808 2.4881302-5.96012998 0-2.26581266-.9046382-4.3883241-2.487443-5.95944795-.1952117-.19377107-.1950777-.50780316.0002993-.70141031s.5120117-.19347426.7072234.00029682c1.7683321 1.75528196 2.7800854 4.12911258 2.7800854 6.66056144 0 2.53182498-1.0120556 4.90597838-2.7808529 6.66132328zm-14.21898205-3.6854911c-.5523759 0-1.00016505-.4441085-1.00016505-.991944v-3.96777631c0-.54783558.44778915-.99194407 1.00016505-.99194407h2.0003301l5.41965617-3.8393633c.44948677-.31842296 1.07413994-.21516983 1.39520191.23062232.12116339.16823446.18629727.36981184.18629727.57655577v12.01603479c0 .5478356-.44778914.9919441-1.00016505.9919441-.20845738 0-.41170538-.0645985-.58133413-.184766l-5.41965617-3.8393633zm0-.991944h2.32084805l5.68047235 4.0241292v-12.01603479l-5.68047235 4.02412928h-2.32084805z" fill-rule="evenodd"/></symbol><symbol id="icon-block" viewBox="0 0 24 24"><path d="m0 0h24v24h-24z" fill-rule="evenodd"/></symbol><symbol id="icon-book" viewBox="0 0 18 18"><path d="m4 13v-11h1v11h11v-11h-13c-.55228475 0-1 .44771525-1 1v10.2675644c.29417337-.1701701.63571286-.2675644 1-.2675644zm12 1h-13c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1h13zm0 3h-13c-1.1045695 0-2-.8954305-2-2v-12c0-1.1045695.8954305-2 2-2h13c.5522847 0 1 .44771525 1 1v14c0 .5522847-.4477153 1-1 1zm-8.5-13h6c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1 2h4c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-4c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-broad" viewBox="0 0 24 24"><path d="m9.18274226 7.81v7.7999954l2.48162734-2.4816273c.3928221-.3928221 1.0219731-.4005617 1.4030652-.0194696.3911301.3911301.3914806 1.0249268-.0001404 1.4165479l-4.17620796 4.1762079c-.39120769.3912077-1.02508144.3916069-1.41671995-.0000316l-4.1763942-4.1763942c-.39122514-.3912251-.39767006-1.0190815-.01657798-1.4001736.39113012-.3911301 1.02337106-.3930364 1.41951349.0031061l2.48183446 2.4818344v-8.7999954c0-.54911294.4426881-.99439484.99778758-.99557515l8.00221246-.00442485c.5522847 0 1 .44771525 1 1s-.4477153 1-1 1z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 20.182742 24.805206)"/></symbol><symbol id="icon-calendar" viewBox="0 0 18 18"><path d="m12.5 0c.2761424 0 .5.21505737.5.49047852v.50952148h2c1.1072288 0 2 .89451376 2 2v12c0 1.1072288-.8945138 2-2 2h-12c-1.1072288 0-2-.8945138-2-2v-12c0-1.1072288.89451376-2 2-2h1v1h-1c-.55393837 0-1 .44579254-1 1v3h14v-3c0-.55393837-.4457925-1-1-1h-2v1.50952148c0 .27088381-.2319336.49047852-.5.49047852-.2761424 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.2319336-.49047852.5-.49047852zm3.5 7h-14v8c0 .5539384.44579254 1 1 1h12c.5539384 0 1-.4457925 1-1zm-11 6v1h-1v-1zm3 0v1h-1v-1zm3 0v1h-1v-1zm-6-2v1h-1v-1zm3 0v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-3-2v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-5.5-9c.27614237 0 .5.21505737.5.49047852v.50952148h5v1h-5v1.50952148c0 .27088381-.23193359.49047852-.5.49047852-.27614237 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.23193359-.49047852.5-.49047852z" fill-rule="evenodd"/></symbol><symbol id="icon-cart" viewBox="0 0 18 18"><path d="m5 14c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm10 0c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm-10 1c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1 1-.4477153 1-1-.44771525-1-1-1zm10 0c-.5522847 0-1 .4477153-1 1s.4477153 1 1 1 1-.4477153 1-1-.4477153-1-1-1zm-12.82032249-15c.47691417 0 .88746157.33678127.98070211.80449199l.23823144 1.19501025 13.36277974.00045554c.5522847.00001882.9999659.44774934.9999659 1.00004222 0 .07084994-.0075361.14150708-.022474.2107727l-1.2908094 5.98534344c-.1007861.46742419-.5432548.80388386-1.0571651.80388386h-10.24805106c-.59173366 0-1.07142857.4477153-1.07142857 1 0 .5128358.41361449.9355072.94647737.9932723l.1249512.0067277h10.35933776c.2749512 0 .4979349.2228539.4979349.4978051 0 .2749417-.2227336.4978951-.4976753.4980063l-10.35959736.0041886c-1.18346732 0-2.14285714-.8954305-2.14285714-2 0-.6625717.34520317-1.24989198.87690425-1.61383592l-1.63768102-8.19004794c-.01312273-.06561364-.01950005-.131011-.0196107-.19547395l-1.71961253-.00064219c-.27614237 0-.5-.22385762-.5-.5 0-.27614237.22385763-.5.5-.5zm14.53193359 2.99950224h-13.11300004l1.20580469 6.02530174c.11024034-.0163252.22327998-.02480398.33844139-.02480398h10.27064786z"/></symbol><symbol id="icon-chevron-less" viewBox="0 0 10 10"><path d="m5.58578644 4-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 -1 -1 0 9 9)"/></symbol><symbol id="icon-chevron-more" viewBox="0 0 10 10"><path d="m5.58578644 6-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4.00000002c-.39052429.3905243-1.02368927.3905243-1.41421356 0s-.39052429-1.02368929 0-1.41421358z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 1)"/></symbol><symbol id="icon-chevron-right" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-circle-fill" viewBox="0 0 16 16"><path d="m8 14c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-circle" viewBox="0 0 16 16"><path d="m8 12c2.209139 0 4-1.790861 4-4s-1.790861-4-4-4-4 1.790861-4 4 1.790861 4 4 4zm0 2c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-citation" viewBox="0 0 18 18"><path d="m8.63593473 5.99995183c2.20913897 0 3.99999997 1.79084375 3.99999997 3.99996146 0 1.40730761-.7267788 2.64486871-1.8254829 3.35783281 1.6240224.6764218 2.8754442 2.0093871 3.4610603 3.6412466l-1.0763845.000006c-.5310008-1.2078237-1.5108121-2.1940153-2.7691712-2.7181346l-.79002167-.329052v-1.023992l.63016577-.4089232c.8482885-.5504661 1.3698342-1.4895187 1.3698342-2.51898361 0-1.65683828-1.3431457-2.99996146-2.99999997-2.99996146-1.65685425 0-3 1.34312318-3 2.99996146 0 1.02946491.52154569 1.96851751 1.36983419 2.51898361l.63016581.4089232v1.023992l-.79002171.329052c-1.25835905.5241193-2.23817037 1.5103109-2.76917113 2.7181346l-1.07638453-.000006c.58561612-1.6318595 1.8370379-2.9648248 3.46106024-3.6412466-1.09870405-.7129641-1.82548287-1.9505252-1.82548287-3.35783281 0-2.20911771 1.790861-3.99996146 4-3.99996146zm7.36897597-4.99995183c1.1018574 0 1.9950893.89353404 1.9950893 2.00274083v5.994422c0 1.10608317-.8926228 2.00274087-1.9950893 2.00274087l-3.0049107-.0009037v-1l3.0049107.00091329c.5490631 0 .9950893-.44783123.9950893-1.00275046v-5.994422c0-.55646537-.4450595-1.00275046-.9950893-1.00275046h-14.00982141c-.54906309 0-.99508929.44783123-.99508929 1.00275046v5.9971821c0 .66666024.33333333.99999036 1 .99999036l2-.00091329v1l-2 .0009037c-1 0-2-.99999041-2-1.99998077v-5.9971821c0-1.10608322.8926228-2.00274083 1.99508929-2.00274083zm-8.5049107 2.9999711c.27614237 0 .5.22385547.5.5 0 .2761349-.22385763.5-.5.5h-4c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm3 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-1c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm4 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238651-.5-.5 0-.27614453.2238576-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-close" viewBox="0 0 16 16"><path d="m2.29679575 12.2772478c-.39658757.3965876-.39438847 1.0328109-.00062148 1.4265779.39651227.3965123 1.03246768.3934888 1.42657791-.0006214l4.27724782-4.27724787 4.2772478 4.27724787c.3965876.3965875 1.0328109.3943884 1.4265779.0006214.3965123-.3965122.3934888-1.0324677-.0006214-1.4265779l-4.27724787-4.2772478 4.27724787-4.27724782c.3965875-.39658757.3943884-1.03281091.0006214-1.42657791-.3965122-.39651226-1.0324677-.39348875-1.4265779.00062148l-4.2772478 4.27724782-4.27724782-4.27724782c-.39658757-.39658757-1.03281091-.39438847-1.42657791-.00062148-.39651226.39651227-.39348875 1.03246768.00062148 1.42657791l4.27724782 4.27724782z" fill-rule="evenodd"/></symbol><symbol id="icon-collections" viewBox="0 0 18 18"><path d="m15 4c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2h1c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-1v-1zm-4-3c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2v-9c0-1.1045695.8954305-2 2-2zm0 1h-8c-.51283584 0-.93550716.38604019-.99327227.88337887l-.00672773.11662113v9c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227zm-1.5 7c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-compare" viewBox="0 0 18 18"><path d="m12 3c3.3137085 0 6 2.6862915 6 6s-2.6862915 6-6 6c-1.0928452 0-2.11744941-.2921742-2.99996061-.8026704-.88181407.5102749-1.90678042.8026704-3.00003939.8026704-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6c1.09325897 0 2.11822532.29239547 3.00096303.80325037.88158756-.51107621 1.90619177-.80325037 2.99903697-.80325037zm-6 1c-2.76142375 0-5 2.23857625-5 5 0 2.7614237 2.23857625 5 5 5 .74397391 0 1.44999672-.162488 2.08451611-.4539116-1.27652344-1.1000812-2.08451611-2.7287264-2.08451611-4.5460884s.80799267-3.44600721 2.08434391-4.5463015c-.63434719-.29121054-1.34037-.4536985-2.08434391-.4536985zm6 0c-.7439739 0-1.4499967.16248796-2.08451611.45391156 1.27652341 1.10008123 2.08451611 2.72872644 2.08451611 4.54608844s-.8079927 3.4460072-2.08434391 4.5463015c.63434721.2912105 1.34037001.4536985 2.08434391.4536985 2.7614237 0 5-2.2385763 5-5 0-2.76142375-2.2385763-5-5-5zm-1.4162763 7.0005324h-3.16744736c.15614659.3572676.35283837.6927622.58425872 1.0006671h1.99892988c.23142036-.3079049.42811216-.6433995.58425876-1.0006671zm.4162763-2.0005324h-4c0 .34288501.0345146.67770871.10025909 1.0011864h3.79948181c.0657445-.32347769.1002591-.65830139.1002591-1.0011864zm-.4158423-1.99953894h-3.16831543c-.13859957.31730812-.24521946.651783-.31578599.99935097h3.79988742c-.0705665-.34756797-.1771864-.68204285-.315786-.99935097zm-1.58295822-1.999926-.08316107.06199199c-.34550042.27081213-.65446126.58611297-.91825862.93727862h2.00044041c-.28418626-.37830727-.6207872-.71499149-.99902072-.99927061z" fill-rule="evenodd"/></symbol><symbol id="icon-download-file" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.5046024 4c.27614237 0 .5.21637201.5.49209595v6.14827645l1.7462789-1.77990922c.1933927-.1971171.5125222-.19455839.7001689-.0069117.1932998.19329992.1910058.50899492-.0027774.70277812l-2.59089271 2.5908927c-.19483374.1948337-.51177825.1937771-.70556873-.0000133l-2.59099079-2.5909908c-.19484111-.1948411-.19043735-.5151448-.00279066-.70279146.19329987-.19329987.50465175-.19237083.70018565.00692852l1.74638684 1.78001764v-6.14827695c0-.27177709.23193359-.49209595.5-.49209595z" fill-rule="evenodd"/></symbol><symbol id="icon-download" viewBox="0 0 16 16"><path d="m12.9975267 12.999368c.5467123 0 1.0024733.4478567 1.0024733 1.000316 0 .5563109-.4488226 1.000316-1.0024733 1.000316h-9.99505341c-.54671233 0-1.00247329-.4478567-1.00247329-1.000316 0-.5563109.44882258-1.000316 1.00247329-1.000316zm-4.9975267-11.999368c.55228475 0 1 .44497754 1 .99589209v6.80214418l2.4816273-2.48241149c.3928222-.39294628 1.0219732-.4006883 1.4030652-.01947579.3911302.39125371.3914806 1.02525073-.0001404 1.41699553l-4.17620792 4.17752758c-.39120769.3913313-1.02508144.3917306-1.41671995-.0000316l-4.17639421-4.17771394c-.39122513-.39134876-.39767006-1.01940351-.01657797-1.40061601.39113012-.39125372 1.02337105-.3931606 1.41951349.00310701l2.48183446 2.48261871v-6.80214418c0-.55001601.44386482-.99589209 1-.99589209z" fill-rule="evenodd"/></symbol><symbol id="icon-editors" viewBox="0 0 18 18"><path d="m8.72592184 2.54588137c-.48811714-.34391207-1.08343326-.54588137-1.72592184-.54588137-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400182l-.79002171.32905522c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274v.9009805h-1v-.9009805c0-2.5479714 1.54557359-4.79153984 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4 1.09079823 0 2.07961816.43662103 2.80122451 1.1446278-.37707584.09278571-.7373238.22835063-1.07530267.40125357zm-2.72592184 14.45411863h-1v-.9009805c0-2.5479714 1.54557359-4.7915398 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.40732121-.7267788 2.64489414-1.8254829 3.3578652 2.2799093.9496145 3.8254829 3.1931829 3.8254829 5.7411543v.9009805h-1v-.9009805c0-2.1155483-1.2760206-4.0125067-3.2099783-4.8180274l-.7900217-.3290552v-1.02400184l.6301658-.40892721c.8482885-.55047139 1.3698342-1.489533 1.3698342-2.51900785 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400184l-.79002171.3290552c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274z" fill-rule="evenodd"/></symbol><symbol id="icon-email" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-.0049107 2.55749512v1.44250488l-7 4-7-4v-1.44250488l7 4z" fill-rule="evenodd"/></symbol><symbol id="icon-error" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm2.8630343 4.71100931-2.8630343 2.86303426-2.86303426-2.86303426c-.39658757-.39658757-1.03281091-.39438847-1.4265779-.00062147-.39651227.39651226-.39348876 1.03246767.00062147 1.4265779l2.86303426 2.86303426-2.86303426 2.8630343c-.39658757.3965875-.39438847 1.0328109-.00062147 1.4265779.39651226.3965122 1.03246767.3934887 1.4265779-.0006215l2.86303426-2.8630343 2.8630343 2.8630343c.3965875.3965876 1.0328109.3943885 1.4265779.0006215.3965122-.3965123.3934887-1.0324677-.0006215-1.4265779l-2.8630343-2.8630343 2.8630343-2.86303426c.3965876-.39658757.3943885-1.03281091.0006215-1.4265779-.3965123-.39651227-1.0324677-.39348876-1.4265779.00062147z" fill-rule="evenodd"/></symbol><symbol id="icon-ethics" viewBox="0 0 18 18"><path d="m6.76384967 1.41421356.83301651-.8330165c.77492941-.77492941 2.03133823-.77492941 2.80626762 0l.8330165.8330165c.3750728.37507276.8837806.58578644 1.4142136.58578644h1.3496361c1.1045695 0 2 .8954305 2 2v1.34963611c0 .53043298.2107137 1.03914081.5857864 1.41421356l.8330165.83301651c.7749295.77492941.7749295 2.03133823 0 2.80626762l-.8330165.8330165c-.3750727.3750728-.5857864.8837806-.5857864 1.4142136v1.3496361c0 1.1045695-.8954305 2-2 2h-1.3496361c-.530433 0-1.0391408.2107137-1.4142136.5857864l-.8330165.8330165c-.77492939.7749295-2.03133821.7749295-2.80626762 0l-.83301651-.8330165c-.37507275-.3750727-.88378058-.5857864-1.41421356-.5857864h-1.34963611c-1.1045695 0-2-.8954305-2-2v-1.3496361c0-.530433-.21071368-1.0391408-.58578644-1.4142136l-.8330165-.8330165c-.77492941-.77492939-.77492941-2.03133821 0-2.80626762l.8330165-.83301651c.37507276-.37507275.58578644-.88378058.58578644-1.41421356v-1.34963611c0-1.1045695.8954305-2 2-2h1.34963611c.53043298 0 1.03914081-.21071368 1.41421356-.58578644zm-1.41421356 1.58578644h-1.34963611c-.55228475 0-1 .44771525-1 1v1.34963611c0 .79564947-.31607052 1.55871121-.87867966 2.12132034l-.8330165.83301651c-.38440512.38440512-.38440512 1.00764896 0 1.39205408l.8330165.83301646c.56260914.5626092.87867966 1.3256709.87867966 2.1213204v1.3496361c0 .5522847.44771525 1 1 1h1.34963611c.79564947 0 1.55871121.3160705 2.12132034.8786797l.83301651.8330165c.38440512.3844051 1.00764896.3844051 1.39205408 0l.83301646-.8330165c.5626092-.5626092 1.3256709-.8786797 2.1213204-.8786797h1.3496361c.5522847 0 1-.4477153 1-1v-1.3496361c0-.7956495.3160705-1.5587112.8786797-2.1213204l.8330165-.83301646c.3844051-.38440512.3844051-1.00764896 0-1.39205408l-.8330165-.83301651c-.5626092-.56260913-.8786797-1.32567087-.8786797-2.12132034v-1.34963611c0-.55228475-.4477153-1-1-1h-1.3496361c-.7956495 0-1.5587112-.31607052-2.1213204-.87867966l-.83301646-.8330165c-.38440512-.38440512-1.00764896-.38440512-1.39205408 0l-.83301651.8330165c-.56260913.56260914-1.32567087.87867966-2.12132034.87867966zm3.58698944 11.4960218c-.02081224.002155-.04199226.0030286-.06345763.002542-.98766446-.0223875-1.93408568-.3063547-2.75885125-.8155622-.23496767-.1450683-.30784554-.4531483-.16277726-.688116.14506827-.2349677.45314827-.3078455.68811595-.1627773.67447084.4164161 1.44758575.6483839 2.25617384.6667123.01759529.0003988.03495764.0017019.05204365.0038639.01713363-.0017748.03452416-.0026845.05212715-.0026845 2.4852814 0 4.5-2.0147186 4.5-4.5 0-1.04888973-.3593547-2.04134635-1.0074477-2.83787157-.1742817-.21419731-.1419238-.5291218.0722736-.70340353.2141973-.17428173.5291218-.14192375.7034035.07227357.7919032.97327203 1.2317706 2.18808682 1.2317706 3.46900153 0 3.0375661-2.4624339 5.5-5.5 5.5-.02146768 0-.04261937-.0013529-.06337445-.0039782zm1.57975095-10.78419583c.2654788.07599731.419084.35281842.3430867.61829728-.0759973.26547885-.3528185.419084-.6182973.3430867-.37560116-.10752146-.76586237-.16587951-1.15568824-.17249193-2.5587807-.00064534-4.58547766 2.00216524-4.58547766 4.49928198 0 .62691557.12797645 1.23496.37274865 1.7964426.11035133.2531347-.0053975.5477984-.25853224.6581497-.25313473.1103514-.54779841-.0053975-.65814974-.2585322-.29947131-.6869568-.45606667-1.43097603-.45606667-2.1960601 0-3.05211432 2.47714695-5.50006595 5.59399617-5.49921198.48576182.00815502.96289603.0795037 1.42238033.21103795zm-1.9766658 6.41091303 2.69835-2.94655317c.1788432-.21040373.4943901-.23598862.7047939-.05714545.2104037.17884318.2359886.49439014.0571454.70479387l-3.01637681 3.34277395c-.18039088.1999106-.48669547.2210637-.69285412.0478478l-1.93095347-1.62240047c-.21213845-.17678204-.24080048-.49206439-.06401844-.70420284.17678204-.21213844.49206439-.24080048.70420284-.06401844z" fill-rule="evenodd"/></symbol><symbol id="icon-expand"><path d="M7.498 11.918a.997.997 0 0 0-.003-1.411.995.995 0 0 0-1.412-.003l-4.102 4.102v-3.51A1 1 0 0 0 .98 10.09.992.992 0 0 0 0 11.092V17c0 .554.448 1.002 1.002 1.002h5.907c.554 0 1.002-.45 1.002-1.003 0-.539-.45-.978-1.006-.978h-3.51zm3.005-5.835a.997.997 0 0 0 .003 1.412.995.995 0 0 0 1.411.003l4.103-4.103v3.51a1 1 0 0 0 1.001 1.006A.992.992 0 0 0 18 6.91V1.002A1 1 0 0 0 17 0h-5.907a1.003 1.003 0 0 0-1.002 1.003c0 .539.45.978 1.006.978h3.51z" fill-rule="evenodd"/></symbol><symbol id="icon-explore" viewBox="0 0 18 18"><path d="m9 17c4.418278 0 8-3.581722 8-8s-3.581722-8-8-8-8 3.581722-8 8 3.581722 8 8 8zm0 1c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9zm0-2.5c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5c2.969509 0 5.400504-2.3575119 5.497023-5.31714844.0090007-.27599565.2400359-.49243782.5160315-.48343711.2759957.0090007.4924378.2400359.4834371.51603155-.114093 3.4985237-2.9869632 6.284554-6.4964916 6.284554zm-.29090657-12.99359748c.27587424-.01216621.50937715.20161139.52154336.47748563.01216621.27587423-.20161139.50937715-.47748563.52154336-2.93195733.12930094-5.25315116 2.54886451-5.25315116 5.49456849 0 .27614237-.22385763.5-.5.5s-.5-.22385763-.5-.5c0-3.48142406 2.74307146-6.34074398 6.20909343-6.49359748zm1.13784138 8.04763908-1.2004882-1.20048821c-.19526215-.19526215-.19526215-.51184463 0-.70710678s.51184463-.19526215.70710678 0l1.20048821 1.2004882 1.6006509-4.00162734-4.50670359 1.80268144-1.80268144 4.50670359zm4.10281269-6.50378907-2.6692597 6.67314927c-.1016411.2541026-.3029834.4554449-.557086.557086l-6.67314927 2.6692597 2.66925969-6.67314926c.10164107-.25410266.30298336-.45544495.55708602-.55708602z" fill-rule="evenodd"/></symbol><symbol id="icon-filter" viewBox="0 0 16 16"><path d="m14.9738641 0c.5667192 0 1.0261359.4477136 1.0261359 1 0 .24221858-.0902161.47620768-.2538899.65849851l-5.6938314 6.34147206v5.49997973c0 .3147562-.1520673.6111434-.4104543.7999971l-2.05227171 1.4999945c-.45337535.3313696-1.09655869.2418269-1.4365902-.1999993-.13321514-.1730955-.20522717-.3836284-.20522717-.5999978v-6.99997423l-5.69383133-6.34147206c-.3731872-.41563511-.32996891-1.0473954.09653074-1.41107611.18705584-.15950448.42716133-.2474224.67571519-.2474224zm-5.9218641 8.5h-2.105v6.491l.01238459.0070843.02053271.0015705.01955278-.0070558 2.0532976-1.4990996zm-8.02585008-7.5-.01564945.00240169 5.83249953 6.49759831h2.313l5.836-6.499z"/></symbol><symbol id="icon-home" viewBox="0 0 18 18"><path d="m9 5-6 6v5h4v-4h4v4h4v-5zm7 6.5857864v4.4142136c0 .5522847-.4477153 1-1 1h-5v-4h-2v4h-5c-.55228475 0-1-.4477153-1-1v-4.4142136c-.25592232 0-.51184464-.097631-.70710678-.2928932l-.58578644-.5857864c-.39052429-.3905243-.39052429-1.02368929 0-1.41421358l8.29289322-8.29289322 8.2928932 8.29289322c.3905243.39052429.3905243 1.02368928 0 1.41421358l-.5857864.5857864c-.1952622.1952622-.4511845.2928932-.7071068.2928932zm-7-9.17157284-7.58578644 7.58578644.58578644.5857864 7-6.99999996 7 6.99999996.5857864-.5857864z" fill-rule="evenodd"/></symbol><symbol id="icon-image" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm-3.49645283 10.1752453-3.89407257 6.7495552c.11705545.048464.24538859.0751995.37998328.0751995h10.60290092l-2.4329715-4.2154691-1.57494129 2.7288098zm8.49779013 6.8247547c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v13.98991071l4.50814957-7.81026689 3.08089884 5.33809539 1.57494129-2.7288097 3.5875735 6.2159812zm-3.0059397-11c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm0 1c-.5522847 0-1 .44771525-1 1s.4477153 1 1 1 1-.44771525 1-1-.4477153-1-1-1z" fill-rule="evenodd"/></symbol><symbol id="icon-info" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm0 7h-1.5l-.11662113.00672773c-.49733868.05776511-.88337887.48043643-.88337887.99327227 0 .47338693.32893365.86994729.77070917.97358929l.1126697.01968298.11662113.00672773h.5v3h-.5l-.11662113.0067277c-.42082504.0488782-.76196299.3590206-.85696816.7639815l-.01968298.1126697-.00672773.1166211.00672773.1166211c.04887817.4208251.35902055.761963.76398144.8569682l.1126697.019683.11662113.0067277h3l.1166211-.0067277c.4973387-.0577651.8833789-.4804365.8833789-.9932723 0-.4733869-.3289337-.8699473-.7707092-.9735893l-.1126697-.019683-.1166211-.0067277h-.5v-4l-.00672773-.11662113c-.04887817-.42082504-.35902055-.76196299-.76398144-.85696816l-.1126697-.01968298zm0-3.25c-.69035594 0-1.25.55964406-1.25 1.25s.55964406 1.25 1.25 1.25 1.25-.55964406 1.25-1.25-.55964406-1.25-1.25-1.25z" fill-rule="evenodd"/></symbol><symbol id="icon-institution" viewBox="0 0 18 18"><path d="m7 16.9998189v-2.0003623h4v2.0003623h2v-3.0005434h-8v3.0005434zm-3-10.00181122h-1.52632364c-.27614237 0-.5-.22389817-.5-.50009056 0-.13995446.05863589-.27350497.16166338-.36820841l1.23156713-1.13206327h-2.36690687v12.00217346h3v-2.0003623h-3v-1.0001811h3v-1.0001811h1v-4.00072448h-1zm10 0v2.00036224h-1v4.00072448h1v1.0001811h3v1.0001811h-3v2.0003623h3v-12.00217346h-2.3695309l1.2315671 1.13206327c.2033191.186892.2166633.50325042.0298051.70660631-.0946863.10304615-.2282126.16169266-.3681417.16169266zm3-3.00054336c.5522847 0 1 .44779634 1 1.00018112v13.00235456h-18v-13.00235456c0-.55238478.44771525-1.00018112 1-1.00018112h3.45499992l4.20535144-3.86558216c.19129876-.17584288.48537447-.17584288.67667324 0l4.2053514 3.86558216zm-4 3.00054336h-8v1.00018112h8zm-2 6.00108672h1v-4.00072448h-1zm-1 0v-4.00072448h-2v4.00072448zm-3 0v-4.00072448h-1v4.00072448zm8-4.00072448c.5522847 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.4477153-1.00018112 1-1.00018112zm-12 0c.55228475 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.44771525-1.00018112 1-1.00018112zm5.99868798-7.81907007-5.24205601 4.81852671h10.48411203zm.00131202 3.81834559c-.55228475 0-1-.44779634-1-1.00018112s.44771525-1.00018112 1-1.00018112 1 .44779634 1 1.00018112-.44771525 1.00018112-1 1.00018112zm-1 11.00199236v1.0001811h2v-1.0001811z" fill-rule="evenodd"/></symbol><symbol id="icon-location" viewBox="0 0 18 18"><path d="m9.39521328 16.2688008c.79596342-.7770119 1.59208152-1.6299956 2.33285652-2.5295081 1.4020032-1.7024324 2.4323601-3.3624519 2.9354918-4.871847.2228715-.66861448.3364384-1.29323246.3364384-1.8674457 0-3.3137085-2.6862915-6-6-6-3.36356866 0-6 2.60156856-6 6 0 .57421324.11356691 1.19883122.3364384 1.8674457.50313169 1.5093951 1.53348863 3.1694146 2.93549184 4.871847.74077492.8995125 1.53689309 1.7524962 2.33285648 2.5295081.13694479.1336842.26895677.2602648.39521328.3793207.12625651-.1190559.25826849-.2456365.39521328-.3793207zm-.39521328 1.7311992s-7-6-7-11c0-4 3.13400675-7 7-7 3.8659932 0 7 3.13400675 7 7 0 5-7 11-7 11zm0-8c-1.65685425 0-3-1.34314575-3-3s1.34314575-3 3-3c1.6568542 0 3 1.34314575 3 3s-1.3431458 3-3 3zm0-1c1.1045695 0 2-.8954305 2-2s-.8954305-2-2-2-2 .8954305-2 2 .8954305 2 2 2z" fill-rule="evenodd"/></symbol><symbol id="icon-minus" viewBox="0 0 16 16"><path d="m2.00087166 7h11.99825664c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-11.99825664c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-newsletter" viewBox="0 0 18 18"><path d="m9 11.8482489 2-1.1428571v-1.7053918h-4v1.7053918zm-3-1.7142857v-2.1339632h6v2.1339632l3-1.71428574v-6.41967746h-12v6.41967746zm10-5.3839632 1.5299989.95624934c.2923814.18273835.4700011.50320827.4700011.8479983v8.44575236c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-8.44575236c0-.34479003.1776197-.66525995.47000106-.8479983l1.52999894-.95624934v-2.75c0-.55228475.44771525-1 1-1h12c.5522847 0 1 .44771525 1 1zm0 1.17924764v3.07075236l-7 4-7-4v-3.07075236l-1 .625v8.44575236c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-8.44575236zm-10-1.92924764h6v1h-6zm-1 2h8v1h-8z" fill-rule="evenodd"/></symbol><symbol id="icon-orcid" viewBox="0 0 18 18"><path d="m9 1c4.418278 0 8 3.581722 8 8s-3.581722 8-8 8-8-3.581722-8-8 3.581722-8 8-8zm-2.90107518 5.2732337h-1.41865256v7.1712107h1.41865256zm4.55867178.02508949h-2.99247027v7.14612121h2.91062487c.7673039 0 1.4476365-.1483432 2.0410182-.445034s1.0511995-.7152915 1.3734671-1.2558144c.3222677-.540523.4833991-1.1603247.4833991-1.85942385 0-.68545815-.1602789-1.30270225-.4808414-1.85175082-.3205625-.54904856-.7707074-.97532211-1.3504481-1.27883343-.5797408-.30351132-1.2413173-.45526471-1.9847495-.45526471zm-.1892674 1.07933542c.7877654 0 1.4143875.22336734 1.8798852.67010873.4654977.44674138.698243 1.05546001.698243 1.82617415 0 .74343221-.2310402 1.34447791-.6931277 1.80315511-.4620874.4586773-1.0750688.6880124-1.8389625.6880124h-1.46810075v-4.98745039zm-5.08652545-3.71099194c-.21825533 0-.410525.08444276-.57681478.25333081-.16628977.16888806-.24943341.36245684-.24943341.58071218 0 .22345188.08314364.41961891.24943341.58850696.16628978.16888806.35855945.25333082.57681478.25333082.233845 0 .43390938-.08314364.60019916-.24943342.16628978-.16628977.24943342-.36375592.24943342-.59240436 0-.233845-.08314364-.43131115-.24943342-.59240437s-.36635416-.24163862-.60019916-.24163862z" fill-rule="evenodd"/></symbol><symbol id="icon-plus" viewBox="0 0 16 16"><path d="m2.00087166 7h4.99912834v-4.99912834c0-.55276616.44386482-1.00087166 1-1.00087166.55228475 0 1 .44463086 1 1.00087166v4.99912834h4.9991283c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-4.9991283v4.9991283c0 .5527662-.44386482 1.0008717-1 1.0008717-.55228475 0-1-.4446309-1-1.0008717v-4.9991283h-4.99912834c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-print" viewBox="0 0 18 18"><path d="m16.0049107 5h-14.00982141c-.54941618 0-.99508929.4467783-.99508929.99961498v6.00077002c0 .5570958.44271433.999615.99508929.999615h1.00491071v-3h12v3h1.0049107c.5494162 0 .9950893-.4467783.9950893-.999615v-6.00077002c0-.55709576-.4427143-.99961498-.9950893-.99961498zm-2.0049107-1v-2.00208688c0-.54777062-.4519464-.99791312-1.0085302-.99791312h-7.9829396c-.55661731 0-1.0085302.44910695-1.0085302.99791312v2.00208688zm1 10v2.0018986c0 1.103521-.9019504 1.9981014-2.0085302 1.9981014h-7.9829396c-1.1092806 0-2.0085302-.8867064-2.0085302-1.9981014v-2.0018986h-1.00491071c-1.10185739 0-1.99508929-.8874333-1.99508929-1.999615v-6.00077002c0-1.10435686.8926228-1.99961498 1.99508929-1.99961498h1.00491071v-2.00208688c0-1.10341695.90195036-1.99791312 2.0085302-1.99791312h7.9829396c1.1092806 0 2.0085302.89826062 2.0085302 1.99791312v2.00208688h1.0049107c1.1018574 0 1.9950893.88743329 1.9950893 1.99961498v6.00077002c0 1.1043569-.8926228 1.999615-1.9950893 1.999615zm-1-3h-10v5.0018986c0 .5546075.44702548.9981014 1.0085302.9981014h7.9829396c.5565964 0 1.0085302-.4491701 1.0085302-.9981014zm-9 1h8v1h-8zm0 2h5v1h-5zm9-5c-.5522847 0-1-.44771525-1-1s.4477153-1 1-1 1 .44771525 1 1-.4477153 1-1 1z" fill-rule="evenodd"/></symbol><symbol id="icon-search" viewBox="0 0 22 22"><path d="M21.697 20.261a1.028 1.028 0 01.01 1.448 1.034 1.034 0 01-1.448-.01l-4.267-4.267A9.812 9.811 0 010 9.812a9.812 9.811 0 1117.43 6.182zM9.812 18.222A8.41 8.41 0 109.81 1.403a8.41 8.41 0 000 16.82z" fill-rule="evenodd"/></symbol><symbol id="icon-social-facebook" viewBox="0 0 24 24"><path d="m6.00368507 20c-1.10660471 0-2.00368507-.8945138-2.00368507-1.9940603v-12.01187942c0-1.10128908.89451376-1.99406028 1.99406028-1.99406028h12.01187942c1.1012891 0 1.9940603.89451376 1.9940603 1.99406028v12.01187942c0 1.1012891-.88679 1.9940603-2.0032184 1.9940603h-2.9570132v-6.1960818h2.0797387l.3114113-2.414723h-2.39115v-1.54164807c0-.69911803.1941355-1.1755439 1.1966615-1.1755439l1.2786739-.00055875v-2.15974763l-.2339477-.02492088c-.3441234-.03134957-.9500153-.07025255-1.6293054-.07025255-1.8435726 0-3.1057323 1.12531866-3.1057323 3.19187953v1.78079225h-2.0850778v2.414723h2.0850778v6.1960818z" fill-rule="evenodd"/></symbol><symbol id="icon-social-twitter" viewBox="0 0 24 24"><path d="m18.8767135 6.87445248c.7638174-.46908424 1.351611-1.21167363 1.6250764-2.09636345-.7135248.43394112-1.50406.74870123-2.3464594.91677702-.6695189-.73342162-1.6297913-1.19486605-2.6922204-1.19486605-2.0399895 0-3.6933555 1.69603749-3.6933555 3.78628909 0 .29642457.0314329.58673729.0942985.8617704-3.06469922-.15890802-5.78835241-1.66547825-7.60988389-3.9574208-.3174714.56076194-.49978171 1.21167363-.49978171 1.90536824 0 1.31404706.65223085 2.47224203 1.64236444 3.15218497-.60350999-.0198635-1.17401554-.1925232-1.67222562-.47366811v.04583885c0 1.83355406 1.27302891 3.36609966 2.96411421 3.71294696-.31118484.0886217-.63651445.1329326-.97441718.1329326-.2357461 0-.47149219-.0229194-.69466516-.0672303.47149219 1.5065703 1.83253297 2.6036468 3.44975116 2.632678-1.2651707 1.0160946-2.85724264 1.6196394-4.5891906 1.6196394-.29861172 0-.59093688-.0152796-.88011875-.0504227 1.63450624 1.0726291 3.57548241 1.6990934 5.66104951 1.6990934 6.79263079 0 10.50641749-5.7711113 10.50641749-10.7751859l-.0094298-.48894775c.7229547-.53478659 1.3516109-1.20250585 1.8419628-1.96190282-.6632323.30100846-1.3751855.50422736-2.1217148.59590507z" fill-rule="evenodd"/></symbol><symbol id="icon-social-youtube" viewBox="0 0 24 24"><path d="m10.1415 14.3973208-.0005625-5.19318431 4.863375 2.60554491zm9.963-7.92753362c-.6845625-.73643756-1.4518125-.73990314-1.803375-.7826454-2.518875-.18714178-6.2971875-.18714178-6.2971875-.18714178-.007875 0-3.7861875 0-6.3050625.18714178-.352125.04274226-1.1188125.04620784-1.8039375.7826454-.5394375.56084773-.7149375 1.8344515-.7149375 1.8344515s-.18 1.49597903-.18 2.99138042v1.4024082c0 1.495979.18 2.9913804.18 2.9913804s.1755 1.2736038.7149375 1.8344515c.685125.7364376 1.5845625.7133337 1.9850625.7901542 1.44.1420891 6.12.1859866 6.12.1859866s3.78225-.005776 6.301125-.1929178c.3515625-.0433198 1.1188125-.0467854 1.803375-.783223.5394375-.5608477.7155-1.8344515.7155-1.8344515s.18-1.4954014.18-2.9913804v-1.4024082c0-1.49540139-.18-2.99138042-.18-2.99138042s-.1760625-1.27360377-.7155-1.8344515z" fill-rule="evenodd"/></symbol><symbol id="icon-subject-medicine" viewBox="0 0 18 18"><path d="m12.5 8h-6.5c-1.65685425 0-3 1.34314575-3 3v1c0 1.6568542 1.34314575 3 3 3h1v-2h-.5c-.82842712 0-1.5-.6715729-1.5-1.5s.67157288-1.5 1.5-1.5h1.5 2 1 2c1.6568542 0 3-1.34314575 3-3v-1c0-1.65685425-1.3431458-3-3-3h-2v2h1.5c.8284271 0 1.5.67157288 1.5 1.5s-.6715729 1.5-1.5 1.5zm-5.5-1v-1h-3.5c-1.38071187 0-2.5-1.11928813-2.5-2.5s1.11928813-2.5 2.5-2.5h1.02786405c.46573528 0 .92507448.10843528 1.34164078.31671843l1.13382424.56691212c.06026365-1.05041141.93116291-1.88363055 1.99667093-1.88363055 1.1045695 0 2 .8954305 2 2h2c2.209139 0 4 1.790861 4 4v1c0 2.209139-1.790861 4-4 4h-2v1h2c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2h-2c0 1.1045695-.8954305 2-2 2s-2-.8954305-2-2h-1c-2.209139 0-4-1.790861-4-4v-1c0-2.209139 1.790861-4 4-4zm0-2v-2.05652691c-.14564246-.03538148-.28733393-.08714006-.42229124-.15461871l-1.15541752-.57770876c-.27771087-.13885544-.583937-.21114562-.89442719-.21114562h-1.02786405c-.82842712 0-1.5.67157288-1.5 1.5s.67157288 1.5 1.5 1.5zm4 1v1h1.5c.2761424 0 .5-.22385763.5-.5s-.2238576-.5-.5-.5zm-1 1v-5c0-.55228475-.44771525-1-1-1s-1 .44771525-1 1v5zm-2 4v5c0 .5522847.44771525 1 1 1s1-.4477153 1-1v-5zm3 2v2h2c.5522847 0 1-.4477153 1-1s-.4477153-1-1-1zm-4-1v-1h-.5c-.27614237 0-.5.2238576-.5.5s.22385763.5.5.5zm-3.5-9h1c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-success" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm3.4860198 4.98163161-4.71802968 5.50657859-2.62834168-2.02300024c-.42862421-.36730544-1.06564993-.30775346-1.42283677.13301307-.35718685.44076653-.29927542 1.0958383.12934879 1.46314377l3.40735508 2.7323063c.42215801.3385221 1.03700951.2798252 1.38749189-.1324571l5.38450527-6.33394549c.3613513-.43716226.3096573-1.09278382-.115462-1.46437175-.4251192-.37158792-1.0626796-.31842941-1.4240309.11873285z" fill-rule="evenodd"/></symbol><symbol id="icon-table" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587l-4.0059107-.001.001.001h-1l-.001-.001h-5l.001.001h-1l-.001-.001-3.00391071.001c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm-11.0059107 5h-3.999v6.9941413c0 .5572961.44630695 1.0058587.99508929 1.0058587h3.00391071zm6 0h-5v8h5zm5.0059107-4h-4.0059107v3h5.001v1h-5.001v7.999l4.0059107.001c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-12.5049107 9c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.22385763-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1.499-5h-5v3h5zm-6 0h-3.00391071c-.54871518 0-.99508929.44887827-.99508929 1.00585866v1.99414134h3.999z" fill-rule="evenodd"/></symbol><symbol id="icon-tick-circle" viewBox="0 0 24 24"><path d="m12 2c5.5228475 0 10 4.4771525 10 10s-4.4771525 10-10 10-10-4.4771525-10-10 4.4771525-10 10-10zm0 1c-4.97056275 0-9 4.02943725-9 9 0 4.9705627 4.02943725 9 9 9 4.9705627 0 9-4.0294373 9-9 0-4.97056275-4.0294373-9-9-9zm4.2199868 5.36606669c.3613514-.43716226.9989118-.49032077 1.424031-.11873285s.4768133 1.02720949.115462 1.46437175l-6.093335 6.94397871c-.3622945.4128716-.9897871.4562317-1.4054264.0971157l-3.89719065-3.3672071c-.42862421-.3673054-.48653564-1.0223772-.1293488-1.4631437s.99421256-.5003185 1.42283677-.1330131l3.11097438 2.6987741z" fill-rule="evenodd"/></symbol><symbol id="icon-tick" viewBox="0 0 16 16"><path d="m6.76799012 9.21106946-3.1109744-2.58349728c-.42862421-.35161617-1.06564993-.29460792-1.42283677.12733148s-.29927541 1.04903009.1293488 1.40064626l3.91576307 3.23873978c.41034319.3393961 1.01467563.2976897 1.37450571-.0948578l6.10568327-6.660841c.3613513-.41848908.3096572-1.04610608-.115462-1.4018218-.4251192-.35571573-1.0626796-.30482786-1.424031.11366122z" fill-rule="evenodd"/></symbol><symbol id="icon-update" viewBox="0 0 18 18"><path d="m1 13v1c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-1h-1v-10h-14v10zm16-1h1v2c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-2h1v-9c0-.55228475.44771525-1 1-1h14c.5522847 0 1 .44771525 1 1zm-1 0v1h-4.5857864l-1 1h-2.82842716l-1-1h-4.58578644v-1h5l1 1h2l1-1zm-13-8h12v7h-12zm1 1v5h10v-5zm1 1h4v1h-4zm0 2h4v1h-4z" fill-rule="evenodd"/></symbol><symbol id="icon-upload" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.85576936 4.14572769c.19483374-.19483375.51177826-.19377714.70556874.00001334l2.59099082 2.59099079c.1948411.19484112.1904373.51514474.0027906.70279143-.1932998.19329987-.5046517.19237083-.7001856-.00692852l-1.74638687-1.7800176v6.14827687c0 .2717771-.23193359.492096-.5.492096-.27614237 0-.5-.216372-.5-.492096v-6.14827641l-1.74627892 1.77990922c-.1933927.1971171-.51252214.19455839-.70016883.0069117-.19329987-.19329988-.19100584-.50899493.00277731-.70277808z" fill-rule="evenodd"/></symbol><symbol id="icon-video" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-8.30912922 2.24944486 4.60460462 2.73982242c.9365543.55726659.9290753 1.46522435 0 2.01804082l-4.60460462 2.7398224c-.93655425.5572666-1.69578148.1645632-1.69578148-.8937585v-5.71016863c0-1.05087579.76670616-1.446575 1.69578148-.89375851zm-.67492769.96085624v5.5750128c0 .2995102-.10753745.2442517.16578928.0847713l4.58452283-2.67497259c.3050619-.17799716.3051624-.21655446 0-.39461026l-4.58452283-2.67497264c-.26630747-.15538481-.16578928-.20699944-.16578928.08477139z" fill-rule="evenodd"/></symbol><symbol id="icon-warning" viewBox="0 0 18 18"><path d="m9 11.75c.69035594 0 1.25.5596441 1.25 1.25s-.55964406 1.25-1.25 1.25-1.25-.5596441-1.25-1.25.55964406-1.25 1.25-1.25zm.41320045-7.75c.55228475 0 1.00000005.44771525 1.00000005 1l-.0034543.08304548-.3333333 4c-.043191.51829212-.47645714.91695452-.99654578.91695452h-.15973424c-.52008864 0-.95335475-.3986624-.99654576-.91695452l-.33333333-4c-.04586475-.55037702.36312325-1.03372649.91350028-1.07959124l.04148683-.00259031zm-.41320045 14c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-left-bullet" viewBox="0 0 8 16"><path d="M3 8l5 5v3L0 8l8-8v3L3 8z"/></symbol><symbol id="icon-chevron-down" viewBox="0 0 16 16"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 3)"/></symbol><symbol id="icon-download-rounded"><path d="M0 13c0-.556.449-1 1.002-1h9.996a.999.999 0 110 2H1.002A1.006 1.006 0 010 13zM7 1v6.8l2.482-2.482c.392-.392 1.022-.4 1.403-.02a1.001 1.001 0 010 1.417l-4.177 4.177a1.001 1.001 0 01-1.416 0L1.115 6.715a.991.991 0 01-.016-1.4 1 1 0 011.42.003L5 7.8V1c0-.55.444-.996 1-.996.552 0 1 .445 1 .996z"/></symbol><symbol id="icon-ext-link" viewBox="0 0 16 16"><path d="M12.9 16H3.1C1.4 16 0 14.6 0 12.9V3.2C0 1.4 1.4 0 3.1 0h3.7v1H3.1C2 1 1 2 1 3.2v9.7C1 14 2 15 3.1 15h9.7c1.2 0 2.1-1 2.1-2.1V8.7h1v4.2c.1 1.7-1.3 3.1-3 3.1z"/><path d="M12.8 2.5l.7.7-9 8.9-.7-.7 9-8.9z"/><path d="M9.7 0L16 6.2V0z"/></symbol><symbol id="icon-remove" viewBox="-296 388 18 18"><path d="M-291.7 396.1h9v2h-9z"/><path d="M-287 405.5c-4.7 0-8.5-3.8-8.5-8.5s3.8-8.5 8.5-8.5 8.5 3.8 8.5 8.5-3.8 8.5-8.5 8.5zm0-16c-4.1 0-7.5 3.4-7.5 7.5s3.4 7.5 7.5 7.5 7.5-3.4 7.5-7.5-3.4-7.5-7.5-7.5z"/></symbol><symbol id="icon-rss" viewBox="0 0 18 18"><path d="m.97480857 6.01583891.11675372.00378391c5.75903295.51984988 10.34261021 5.10537458 10.85988231 10.86480098.0494035.5500707-.3564674 1.0360406-.906538 1.0854441-.5500707.0494036-1.0360406-.3564673-1.08544412-.906538-.43079083-4.7965248-4.25151132-8.61886853-9.04770289-9.05180573-.55004837-.04965115-.95570047-.53580366-.90604933-1.08585203.04610464-.5107592.46858035-.89701345.96909831-.90983323zm1.52519143 6.95474179c1.38071187 0 2.5 1.1192881 2.5 2.5s-1.11928813 2.5-2.5 2.5-2.5-1.1192881-2.5-2.5 1.11928813-2.5 2.5-2.5zm-1.43253846-12.96884168c9.09581416.53242539 16.37540296 7.8163886 16.90205336 16.91294558.0319214.5513615-.389168 1.0242056-.9405294 1.056127-.5513615.0319214-1.0242057-.389168-1.0561271-.9405294-.4679958-8.08344784-6.93949306-14.55883389-15.02226722-15.03196077-.55134101-.03227286-.97212889-.50538538-.93985602-1.05672639.03227286-.551341.50538538-.97212888 1.05672638-.93985602z" fill-rule="evenodd"/></symbol><symbol id="icon-springer-arrow-left"><path d="M15 7a1 1 0 000-2H3.385l2.482-2.482a.994.994 0 00.02-1.403 1.001 1.001 0 00-1.417 0L.294 5.292a1.001 1.001 0 000 1.416l4.176 4.177a.991.991 0 001.4.016 1 1 0 00-.003-1.42L3.385 7H15z"/></symbol><symbol id="icon-springer-arrow-right"><path d="M1 7a1 1 0 010-2h11.615l-2.482-2.482a.994.994 0 01-.02-1.403 1.001 1.001 0 011.417 0l4.176 4.177a1.001 1.001 0 010 1.416l-4.176 4.177a.991.991 0 01-1.4.016 1 1 0 01.003-1.42L12.615 7H1z"/></symbol><symbol id="icon-springer-collections" viewBox="3 3 32 32"><path fill-rule="evenodd" d="M25.583333,30.1249997 L25.583333,7.1207574 C25.583333,7.10772495 25.579812,7.10416665 25.5859851,7.10416665 L6.10400517,7.10571021 L6.10400517,30.1355179 C6.10400517,31.1064087 6.89406744,31.8958329 7.86448169,31.8958329 L26.057145,31.8958329 C25.7558021,31.374901 25.583333,30.7700915 25.583333,30.1249997 Z M4.33333333,30.1355179 L4.33333333,7.10571021 C4.33333333,6.12070047 5.12497502,5.33333333 6.10151452,5.33333333 L25.5859851,5.33333333 C26.5617372,5.33333333 27.3541664,6.13359035 27.3541664,7.1207574 L27.3541664,12.4166666 L32.6666663,12.4166666 L32.6666663,30.1098941 C32.6666663,32.0694626 31.0857174,33.6666663 29.1355179,33.6666663 L7.86448169,33.6666663 C5.91736809,33.6666663 4.33333333,32.0857174 4.33333333,30.1355179 Z M27.3541664,14.1874999 L27.3541664,30.1249997 C27.3541664,31.1030039 28.1469954,31.8958329 29.1249997,31.8958329 C30.1030039,31.8958329 30.8958329,31.1030039 30.8958329,30.1249997 L30.8958329,14.1874999 L27.3541664,14.1874999 Z M9.64583326,10.6458333 L22.0416665,10.6458333 L22.0416665,17.7291665 L9.64583326,17.7291665 L9.64583326,10.6458333 Z M11.4166666,12.4166666 L11.4166666,15.9583331 L20.2708331,15.9583331 L20.2708331,12.4166666 L11.4166666,12.4166666 Z M9.64583326,19.4999998 L22.0416665,19.4999998 L22.0416665,21.2708331 L9.64583326,21.2708331 L9.64583326,19.4999998 Z M9.64583326,23.0416665 L22.0416665,23.0416665 L22.0416665,24.8124997 L9.64583326,24.8124997 L9.64583326,23.0416665 Z M9.64583326,26.583333 L22.0416665,26.583333 L22.0416665,28.3541664 L9.64583326,28.3541664 L9.64583326,26.583333 Z"/></symbol><symbol id="icon-springer-download" viewBox="-301 390 9 14"><path d="M-301 395.6l4.5 5.1 4.5-5.1h-3V390h-3v5.6h-3zm0 6.5h9v1.9h-9z"/></symbol><symbol id="icon-springer-info" viewBox="0 0 24 24"><g id="V&I" stroke="none" stroke-width="1" fill-rule="evenodd"><g id="info" fill-rule="nonzero"><path d="M12,0 C18.627417,0 24,5.372583 24,12 C24,18.627417 18.627417,24 12,24 C5.372583,24 0,18.627417 0,12 C0,5.372583 5.372583,0 12,0 Z M12.5540543,9.1 L11.5540543,9.1 C11.0017696,9.1 10.5540543,9.54771525 10.5540543,10.1 L10.5540543,10.1 L10.5540543,18.1 C10.5540543,18.6522847 11.0017696,19.1 11.5540543,19.1 L11.5540543,19.1 L12.5540543,19.1 C13.1063391,19.1 13.5540543,18.6522847 13.5540543,18.1 L13.5540543,18.1 L13.5540543,10.1 C13.5540543,9.54771525 13.1063391,9.1 12.5540543,9.1 L12.5540543,9.1 Z M12,5 C11.5356863,5 11.1529412,5.14640523 10.8517647,5.43921569 C10.5505882,5.73202614 10.4,6.11546841 10.4,6.58954248 C10.4,7.06361656 10.5505882,7.45054466 10.8517647,7.7503268 C11.1529412,8.05010893 11.5356863,8.2 12,8.2 C12.4768627,8.2 12.8627451,8.05010893 13.1576471,7.7503268 C13.452549,7.45054466 13.6,7.06361656 13.6,6.58954248 C13.6,6.11546841 13.452549,5.73202614 13.1576471,5.43921569 C12.8627451,5.14640523 12.4768627,5 12,5 Z" id="Combined-Shape"/></g></g></symbol><symbol id="icon-springer-tick-circle" viewBox="0 0 24 24"><g id="Page-1" stroke="none" stroke-width="1" fill-rule="evenodd"><g id="springer-tick-circle" fill-rule="nonzero"><path d="M12,24 C5.372583,24 0,18.627417 0,12 C0,5.372583 5.372583,0 12,0 C18.627417,0 24,5.372583 24,12 C24,18.627417 18.627417,24 12,24 Z M7.657,10.79 C7.45285634,10.6137568 7.18569967,10.5283283 6.91717333,10.5534259 C6.648647,10.5785236 6.40194824,10.7119794 6.234,10.923 C5.87705269,11.3666969 5.93445559,12.0131419 6.364,12.387 L10.261,15.754 C10.6765468,16.112859 11.3037113,16.0695601 11.666,15.657 L17.759,8.713 C18.120307,8.27302248 18.0695334,7.62621189 17.644,7.248 C17.4414817,7.06995024 17.1751516,6.9821166 16.9064461,7.00476032 C16.6377406,7.02740404 16.3898655,7.15856958 16.22,7.368 L10.768,13.489 L7.657,10.79 Z" id="path-1"/></g></g></symbol><symbol id="icon-updates" viewBox="0 0 18 18"><g fill-rule="nonzero"><path d="M16.98 3.484h-.48c-2.52-.058-5.04 1.161-7.44 2.903-2.46-1.8-4.74-2.903-8.04-2.903-.3 0-.54.29-.54.58v9.813c0 .29.24.523.54.581 2.76.348 4.86 1.045 7.62 2.903.24.116.54.116.72 0 2.76-1.858 4.86-2.555 7.62-2.903.3-.058.54-.29.54-.58V4.064c0-.29-.24-.523-.54-.581zm-15.3 1.22c2.34 0 4.86 1.509 6.72 2.786v8.478c-2.34-1.394-4.38-2.09-6.72-2.439V4.703zm14.58 8.767c-2.34.348-4.38 1.045-6.72 2.439V7.374C12 5.632 14.1 4.645 16.26 4.645v8.826z"/><path d="M9 .058c-1.56 0-2.76 1.22-2.76 2.671C6.24 4.181 7.5 5.4 9 5.4c1.5 0 2.76-1.22 2.76-2.671 0-1.452-1.2-2.67-2.76-2.67zm0 4.413c-.96 0-1.8-.755-1.8-1.742C7.2 1.8 7.98.987 9 .987s1.8.755 1.8 1.742c0 .93-.84 1.742-1.8 1.742z"/></g></symbol><symbol id="icon-checklist-banner" viewBox="0 0 56.69 56.69"><path style="fill:none" d="M0 0h56.69v56.69H0z"/><clipPath id="b"><use xlink:href="#a" style="overflow:visible"/></clipPath><path d="M21.14 34.46c0-6.77 5.48-12.26 12.24-12.26s12.24 5.49 12.24 12.26-5.48 12.26-12.24 12.26c-6.76-.01-12.24-5.49-12.24-12.26zm19.33 10.66 10.23 9.22s1.21 1.09 2.3-.12l2.09-2.32s1.09-1.21-.12-2.3l-10.23-9.22m-19.29-5.92c0-4.38 3.55-7.94 7.93-7.94s7.93 3.55 7.93 7.94c0 4.38-3.55 7.94-7.93 7.94-4.38-.01-7.93-3.56-7.93-7.94zm17.58 12.99 4.14-4.81" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round"/><path d="M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5m14.42-5.2V4.86s0-2.93-2.93-2.93H4.13s-2.93 0-2.93 2.93v37.57s0 2.93 2.93 2.93h15.01M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round;stroke-linejoin:round"/></symbol><symbol id="icon-submit-closed" viewBox="0 0 18 18"><path d="m15 0c1.1045695 0 2 .8954305 2 2v4.5c0 .27614237-.2238576.5-.5.5s-.5-.22385763-.5-.5v-4.5c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-9v3c0 1.1045695-.8954305 2-2 2h-3v10c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h4.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-4.5c-1.1045695 0-2-.8954305-2-2v-10.17157288c0-.53043297.21071368-1.0391408.58578644-1.41421356l3.82842712-3.82842712c.37507276-.37507276.88378059-.58578644 1.41421356-.58578644zm-2.5 7c3.0375661 0 5.5 2.46243388 5.5 5.5 0 3.0375661-2.4624339 5.5-5.5 5.5-3.03756612 0-5.5-2.4624339-5.5-5.5 0-3.03756612 2.46243388-5.5 5.5-5.5zm0 1c-2.4852814 0-4.5 2.0147186-4.5 4.5s2.0147186 4.5 4.5 4.5 4.5-2.0147186 4.5-4.5-2.0147186-4.5-4.5-4.5zm2.3087379 2.1912621c.2550161.2550162.2550161.668479 0 .9234952l-1.3859024 1.3845831 1.3859024 1.3859023c.2550161.2550162.2550161.668479 0 .9234952-.2550162.2550161-.668479.2550161-.9234952 0l-1.3859023-1.3859024-1.3845831 1.3859024c-.2550162.2550161-.668479.2550161-.9234952 0-.25501614-.2550162-.25501614-.668479 0-.9234952l1.3845831-1.3859023-1.3845831-1.3845831c-.25501614-.2550162-.25501614-.668479 0-.9234952.2550162-.25501614.668479-.25501614.9234952 0l1.3845831 1.3845831 1.3859023-1.3845831c.2550162-.25501614.668479-.25501614.9234952 0zm-9.8087379-8.7782621-3.587 3.587h2.587c.55228475 0 1-.44771525 1-1z"/></symbol><symbol id="icon-submit-open" viewBox="0 0 18 18"><path d="m15 0c1.1045695 0 2 .8954305 2 2v5.5c0 .27614237-.2238576.5-.5.5s-.5-.22385763-.5-.5v-5.5c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-9v3c0 1.1045695-.8954305 2-2 2h-3v10c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h7.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-7.5c-1.1045695 0-2-.8954305-2-2v-10.17157288c0-.53043297.21071368-1.0391408.58578644-1.41421356l3.82842712-3.82842712c.37507276-.37507276.88378059-.58578644 1.41421356-.58578644zm-.5442863 8.18867991 3.3545404 3.35454039c.2508994.2508994.2538696.6596433.0035959.909917-.2429543.2429542-.6561449.2462671-.9065387-.0089489l-2.2609825-2.3045251.0010427 7.2231989c0 .3569916-.2898381.6371378-.6473715.6371378-.3470771 0-.6473715-.2852563-.6473715-.6371378l-.0010428-7.2231995-2.2611222 2.3046654c-.2531661.2580415-.6562868.2592444-.9065605.0089707-.24295423-.2429542-.24865597-.6576651.0036132-.9099343l3.3546673-3.35466731c.2509089-.25090888.6612706-.25227691.9135302-.00001728zm-.9557137-3.18867991c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm-8.5-3.587-3.587 3.587h2.587c.55228475 0 1-.44771525 1-1zm8.5 1.587c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z"/></symbol><symbol id="icon-submit-upcoming" viewBox="0 0 18 18"><path d="m15 0c1.1045695 0 2 .8954305 2 2v4.5c0 .27614237-.2238576.5-.5.5s-.5-.22385763-.5-.5v-4.5c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-9v3c0 1.1045695-.8954305 2-2 2h-3v10c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h4.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-4.5c-1.1045695 0-2-.8954305-2-2v-10.17157288c0-.53043297.21071368-1.0391408.58578644-1.41421356l3.82842712-3.82842712c.37507276-.37507276.88378059-.58578644 1.41421356-.58578644zm-2.5 7c3.0375661 0 5.5 2.46243388 5.5 5.5 0 3.0375661-2.4624339 5.5-5.5 5.5-3.03756612 0-5.5-2.4624339-5.5-5.5 0-1.6607442.73606908-3.14957021 1.89976608-4.15803695l-1.51549374.02214397c-.27613212.00263356-.49998143-.22483432-.49998143-.49020681 0-.24299316.17766103-.44509007.40961587-.48700057l.08928713-.00797472h2.66407569c.2449213 0 .4486219.17766776.490865.40963137l.008038.08929051v2.6642143c0 .275547-.2296028.4989219-.4949753.4989219-.24299317 0-.44342617-.1744719-.4830969-.4093269l-.00710993-.0906783.01983146-1.46576707c-.96740882.82538117-1.58082193 2.05345007-1.58082193 3.42478927 0 2.4852814 2.0147186 4.5 4.5 4.5s4.5-2.0147186 4.5-4.5-2.0147186-4.5-4.5-4.5c-.7684937 0-.7684937-1 0-1zm0 2.85c.3263501 0 .5965265.2405082.6429523.5539478l.0070477.0960522v1.731l.8096194.8093806c.2284567.2284567.2513024.5846637.068537.8386705l-.068537.0805683c-.2284567.2284567-.5846637.2513024-.8386705.068537l-.0805683-.068537-.9707107-.9707107c-.1125218-.1125218-.1855975-.257116-.2103268-.412296l-.0093431-.1180341v-1.9585786c0-.3589851.2910149-.65.65-.65zm-7.5-8.437-3.587 3.587h2.587c.55228475 0 1-.44771525 1-1z"/></symbol><symbol id="icon-facebook-bordered" viewBox="463.812 263.868 32 32"><path d="M479.812,263.868c-8.837,0-16,7.163-16,16s7.163,16,16,16s16-7.163,16-16S488.649,263.868,479.812,263.868z M479.812,293.868c-7.732,0-14-6.269-14-14s6.268-14,14-14s14,6.269,14,14S487.545,293.868,479.812,293.868z"/><path d="M483.025,280.48l0.32-2.477h-2.453v-1.582c0-0.715,0.199-1.207,1.227-1.207h1.311v-2.213 c-0.227-0.029-1.003-0.098-1.907-0.098c-1.894,0-3.186,1.154-3.186,3.271v1.826h-2.142v2.477h2.142v6.354h2.557v-6.354 L483.025,280.48L483.025,280.48z"/></symbol><symbol id="icon-twitter-bordered" viewBox="463.812 263.868 32 32"><g><path d="M486.416,276.191c-0.483,0.215-1.007,0.357-1.554,0.429c0.558-0.338,0.991-0.868,1.19-1.502 c-0.521,0.308-1.104,0.536-1.72,0.657c-0.494-0.526-1.2-0.854-1.979-0.854c-1.496,0-2.711,1.213-2.711,2.71 c0,0.212,0.023,0.419,0.069,0.616c-2.252-0.111-4.25-1.19-5.586-2.831c-0.231,0.398-0.365,0.866-0.365,1.361 c0,0.94,0.479,1.772,1.204,2.257c-0.441-0.015-0.861-0.138-1.227-0.339v0.031c0,1.314,0.937,2.41,2.174,2.656 c-0.227,0.062-0.47,0.098-0.718,0.098c-0.171,0-0.343-0.018-0.511-0.049c0.35,1.074,1.347,1.859,2.531,1.883 c-0.928,0.726-2.095,1.16-3.366,1.16c-0.22,0-0.433-0.014-0.644-0.037c1.2,0.768,2.621,1.215,4.155,1.215 c4.983,0,7.71-4.129,7.71-7.711c0-0.115-0.004-0.232-0.006-0.351C485.592,277.212,486.054,276.734,486.416,276.191z"/></g><path d="M479.812,263.868c-8.837,0-16,7.163-16,16s7.163,16,16,16s16-7.163,16-16S488.649,263.868,479.812,263.868z M479.812,293.868c-7.732,0-14-6.269-14-14s6.268-14,14-14s14,6.269,14,14S487.545,293.868,479.812,293.868z"/></symbol><symbol id="icon-weibo-bordered" viewBox="463.812 263.868 32 32"><path d="M479.812,263.868c-8.838,0-16,7.163-16,16s7.162,16,16,16c8.837,0,16-7.163,16-16S488.649,263.868,479.812,263.868z M479.812,293.868c-7.732,0-14-6.269-14-14s6.268-14,14-14c7.731,0,14,6.269,14,14S487.545,293.868,479.812,293.868z"/><g><path d="M478.552,285.348c-2.616,0.261-4.876-0.926-5.044-2.649c-0.167-1.722,1.814-3.33,4.433-3.588 c2.609-0.263,4.871,0.926,5.041,2.647C483.147,283.479,481.164,285.089,478.552,285.348 M483.782,279.63 c-0.226-0.065-0.374-0.109-0.259-0.403c0.25-0.639,0.276-1.188,0.005-1.581c-0.515-0.734-1.915-0.693-3.521-0.021 c0,0-0.508,0.224-0.378-0.181c0.247-0.798,0.209-1.468-0.178-1.852c-0.87-0.878-3.194,0.032-5.183,2.027 c-1.489,1.494-2.357,3.082-2.357,4.453c0,2.619,3.354,4.213,6.631,4.213c4.297,0,7.154-2.504,7.154-4.493 C485.697,280.594,484.689,279.911,483.782,279.63"/><path d="M486.637,274.833c-1.039-1.154-2.57-1.592-3.982-1.291l0,0c-0.325,0.068-0.532,0.391-0.465,0.72 c0.068,0.328,0.391,0.537,0.72,0.466c1.005-0.215,2.092,0.104,2.827,0.92c0.736,0.818,0.938,1.939,0.625,2.918l0,0 c-0.102,0.318,0.068,0.661,0.39,0.762c0.32,0.104,0.658-0.069,0.763-0.391v-0.001C487.953,277.558,487.674,275.985,486.637,274.833 "/><path d="M485.041,276.276c-0.504-0.562-1.25-0.774-1.938-0.63c-0.279,0.06-0.461,0.339-0.396,0.621 c0.062,0.281,0.335,0.461,0.617,0.398l0,0c0.336-0.071,0.702,0.03,0.947,0.307s0.312,0.649,0.207,0.979l0,0 c-0.089,0.271,0.062,0.565,0.336,0.654c0.274,0.09,0.564-0.062,0.657-0.336C485.686,277.604,485.549,276.837,485.041,276.276"/><path d="M478.694,282.227c-0.09,0.156-0.293,0.233-0.451,0.166c-0.151-0.062-0.204-0.235-0.115-0.389 c0.093-0.155,0.284-0.229,0.44-0.168C478.725,281.892,478.782,282.071,478.694,282.227 M477.862,283.301 c-0.253,0.405-0.795,0.58-1.202,0.396c-0.403-0.186-0.521-0.655-0.27-1.051c0.248-0.39,0.771-0.566,1.176-0.393 C477.979,282.423,478.109,282.889,477.862,283.301 M478.812,280.437c-1.244-0.326-2.65,0.294-3.19,1.396 c-0.553,1.119-0.021,2.369,1.236,2.775c1.303,0.42,2.84-0.225,3.374-1.436C480.758,281.989,480.1,280.77,478.812,280.437"/></g></symbol></svg> </div> <div class="u-vh-full"> <a class="c-skip-link" href="#main-content">Skip to main content</a> <div class="u-hide u-show-following-ad"></div> <aside class="adsbox c-ad c-ad--728x90" data-component-mpu> <div class="c-ad__inner"> <p class="c-ad__label">Advertisement</p> <div id="div-gpt-ad-LB1" data-ad-type="LB1" data-test="LB1-ad" data-pa11y-ignore data-gpt data-gpt-unitpath="/270604982/bmc/genomebiology/articles" data-gpt-sizes="728x90,970x90" data-gpt-targeting="pos=LB1;doi=10.1186/gb-2011-12-7-226;type=article;kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein;pmc=L32030,B12008,L32020,L32010,L15001,L21001;" > <noscript> <a href="//pubads.g.doubleclick.net/gampad/jump?iu=/270604982/bmc/genomebiology/articles&sz=728x90,970x90&pos=LB1&doi=10.1186/gb-2011-12-7-226&type=article&kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein&pmc=L32030,B12008,L32020,L32010,L15001,L21001&"> <img data-test="gpt-advert-fallback-img" src="//pubads.g.doubleclick.net/gampad/ad?iu=/270604982/bmc/genomebiology/articles&sz=728x90,970x90&pos=LB1&doi=10.1186/gb-2011-12-7-226&type=article&kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein&pmc=L32030,B12008,L32020,L32010,L15001,L21001&" alt="Advertisement" width="728" height="90"> </a> </noscript> </div> </div> </aside> <div id="membership-message-loader-desktop" class="placeholder" data-placeholder="/placeholder/v1/membership/message"></div> <div id="top" class="u-position-relative"> <header class="c-header" data-test="publisher-header"> <div class="c-header__container"> <div class="c-header__brand u-mr-48" itemscope itemtype="http://schema.org/Organization" data-test="navbar-logo-header"> <div class="c-logo"> <a href="https://www.biomedcentral.com" itemprop="url"> <img alt="BMC" itemprop="logo" width="76" height="18" role="img" src=/static/images/bmc/logos/logo-bmc-white-flagship-6c54473310.svg> <div class="c-logo__strapline"> <img alt="Part of Springer Nature" width="173" height="16" role="img" src=/static/images/bmc/logos/logo-bmc-white-strapline-sn-f224388d67.svg> </div> </a> </div> </div> <div class="c-header__navigation"> <button type="button" class="c-header__link u-button-reset u-mr-24" data-expander data-expander-target="#publisher-header-search" data-expander-autofocus="firstTabbable" data-test="header-search-button" aria-controls="publisher-header-search" aria-expanded="false"> <span class="u-display-flex u-align-items-center"> <span>Search</span> <svg class="u-icon u-flex-static u-ml-8" aria-hidden="true" focusable="false"> <use xlink:href="#icon-search"></use> </svg> </span> </button> <nav> <ul class="c-header__menu" data-enhanced-menu data-test="publisher-navigation"> <li class="c-header__item u-hide-at-lt-lg"> <a class="c-header__link" href="//www.biomedcentral.com/journals"> Explore journals </a> </li> <li class="c-header__item u-hide-at-lt-lg"> <a class="c-header__link" href="//www.biomedcentral.com/getpublished"> Get published </a> </li> <li class="c-header__item u-hide-at-lt-lg"> <a class="c-header__link" href="//www.biomedcentral.com/about"> About BMC </a> </li> <li class="c-header__item"> <a data-enhanced-account class="c-header__link" href="https://www.biomedcentral.com/account" data-test="login-link"> My account </a> </li> </ul> </nav> </div> </div> </header> <div class="c-popup-search u-js-hide" id="publisher-header-search"> <div class="u-container"> <div class="c-popup-search__container"> <div class="ctx-search"> <form role="search" class="c-form-field js-skip-validation" method="GET" action="//www.biomedcentral.com/search" data-track="search" data-track-context="pop out website-wide search in bmc website header" data-track-category="Search and Results" data-track-action="Submit search" data-dynamic-track-label data-track-label="" data-test="global-search"> <label for="publisherSearch" class="c-form-field__label">Search all BMC articles</label> <div class="u-display-flex"> <input id="publisherSearch" class="c-form-field__input" data-search-input autocomplete="off" role="textbox" data-test="search-input" name="query" type="text" value=""/> <div> <button class="u-button" type="submit" data-test="search-submit-button"> <span class="u-visually-hidden">Search</span> <svg class="u-icon u-flex-static" width="16" height="16" aria-hidden="true" focusable="false"> <use xlink:href="#icon-search"></use> </svg> </button> </div> </div> <input type="hidden" name="searchType" value="publisherSearch"/> </form> </div> </div> </div> </div> </div> <header class="c-journal-header c-journal-header--genome-biology ctx-journal-header"> <div class="u-container"> <div class="c-journal-header__inner c-journal-header__inner--featured-journal"> <div class="c-journal-title" id="journalTitle"> <a href="/"> <span class="c-journal-title__text u-visually-hidden">Genome Biology</span> <div class="c-journal-title__featured-journal-lines c-journal-title__featured-journal-lines--genome-biology"> <img src=/static/images/bmc/logos/genome-biology-logo-cf72c0ec54.svg class="c-journal-title__featured-journal-logo" alt="Genome Biology logo" itemprop="logo" role="img"> </div> </a> </div> </div> </div> <div class="c-navbar c-navbar--with-submit-button"> <div class="c-navbar__container"> <div class="c-navbar__content"> <nav class="c-navbar__nav"> <ul class="c-navbar__nav c-navbar__nav--journal" role="menu" data-test="site-navigation"> <li class="c-navbar__item" role="menuitem"> <a class="c-navbar__link" data-track="click" data-track-category="Home" data-track-action="Clicked journal navigation link" href='/'>Home</a> </li> <li class="c-navbar__item" role="menuitem"> <a class="c-navbar__link" data-track="click" data-track-category="About" data-track-action="Clicked journal navigation link" href='/about'>About</a> </li> <li class="c-navbar__item" role="menuitem"> <a class="c-navbar__link c-navbar__link--is-shown" data-track="click" data-track-category="Articles" data-track-action="Clicked journal navigation link" href='/articles'>Articles</a> </li> <li class="c-navbar__item" role="menuitem"> <a class="c-navbar__link" data-track="click" data-track-category="Submission Guidelines" data-track-action="Clicked journal navigation link" href='/submission-guidelines'>Submission Guidelines</a> </li> <li class="c-navbar__item" role="menuitem"> <a class="c-navbar__link" data-track="click" data-track-category="Collections" data-track-action="Clicked journal navigation link" href='/articles/collections'>Collections</a> </li> <li class="c-navbar__item" role="menuitem" data-test="journal-header-submit-button"> <div class=""> <a class="u-button u-button--tertiary u-button--alt-colour-on-mobile" href="https://submission.springernature.com/new-submission/13059/3" data-track="click_submit_manuscript" data-track-action="manuscript submission" data-track-category="article" data-track-label="button in journal nav" data-track-context="journal header on article page" data-track-external data-test="submit-manuscript-button">Submit manuscript<svg class="u-ml-8" width="15" height="16" aria-hidden="true" focusable="false"><use xlink:href="#icon-submit-open"></use></svg></a> </div> </li> </ul> </nav> </div> </div> </div> <div class="c-journal-header__identity c-journal-header__identity--featured-journal"> </div> </header> <div class="u-container u-mt-32 u-mb-32 u-clearfix" id="main-content" data-component="article-container"> <main class="c-article-main-column u-float-left js-main-column" data-track-component="article body"> <div class="c-context-bar u-hide" data-test="context-bar" data-context-bar aria-hidden="true"> <div class="c-context-bar__container u-container" data-track-context="sticky banner"> <div class="c-context-bar__title"> Atg8: an autophagy-related ubiquitin-like protein family </div> <div class="c-pdf-container"> <div class="c-pdf-download u-clear-both"> <a href="//genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2011-12-7-226.pdf" class="u-button u-button--full-width u-button--primary u-justify-content-space-between c-pdf-download__link" data-article-pdf="true" data-readcube-pdf-url="true" data-test="pdf-link" data-draft-ignore="true" data-track="content_download" data-track-type="article pdf download" data-track-action="download pdf" data-track-label="link" data-track-external download> <span class="c-pdf-download__text">Download PDF</span> <svg aria-hidden="true" focusable="false" width="16" height="16" class="u-icon"><use xlink:href="#icon-download"/></svg> </a> </div> </div> </div> </div> <div class="c-pdf-button__container u-hide-at-lg js-context-bar-sticky-point-mobile"> <div class="c-pdf-container" data-track-context="article body"> <div class="c-pdf-download u-clear-both"> <a href="//genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2011-12-7-226.pdf" class="u-button u-button--full-width u-button--primary u-justify-content-space-between c-pdf-download__link" data-article-pdf="true" data-readcube-pdf-url="true" data-test="pdf-link" data-draft-ignore="true" data-track="content_download" data-track-type="article pdf download" data-track-action="download pdf" data-track-label="link" data-track-external download> <span class="c-pdf-download__text">Download PDF</span> <svg aria-hidden="true" focusable="false" width="16" height="16" class="u-icon"><use xlink:href="#icon-download"/></svg> </a> </div> </div> </div> <article lang="en"> <div class="c-article-header"> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Protein family review</li> <li class="c-article-identifiers__item">Published: <time datetime="2011-07-27">27 July 2011</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">Atg8: an autophagy-related ubiquitin-like protein family</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Tomer-Shpilka-Aff1" data-author-popup="auth-Tomer-Shpilka-Aff1" data-author-search="Shpilka, Tomer">Tomer Shpilka</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Hilla-Weidberg-Aff1" data-author-popup="auth-Hilla-Weidberg-Aff1" data-author-search="Weidberg, Hilla">Hilla Weidberg</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Shmuel-Pietrokovski-Aff2" data-author-popup="auth-Shmuel-Pietrokovski-Aff2" data-author-search="Pietrokovski, Shmuel" data-corresp-id="c1">Shmuel Pietrokovski<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 4 authors for this article" title="Show all 4 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Zvulun-Elazar-Aff1" data-author-popup="auth-Zvulun-Elazar-Aff1" data-author-search="Elazar, Zvulun" data-corresp-id="c2">Zvulun Elazar<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Genome Biology</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 12</b>, Article number: <span data-test="article-number">226</span> (<span data-test="article-publication-year">2011</span>) <a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">30k <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="citation-count"> <p class="c-article-metrics-bar__count">386 <span class="c-article-metrics-bar__label">Citations</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">6 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/10.1186/gb-2011-12-7-226/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </div> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective.</p></div></div></section> <section data-title="Gene organization and evolutionary history"><div class="c-article-section" id="Sec1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec1">Gene organization and evolutionary history</h2><div class="c-article-section__content" id="Sec1-content"><p>Autophagy-related 8 proteins (Atg8s) are one of the 62 highly conserved eukaryote-specific protein families [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Wood V, Gwilliam R, Rajandream MA, Lyne M, Lyne R, Stewart A, Sgouros J, Peat N, Hayles J, Baker S, Basham D, Bowman S, Brooks K, Brown D, Brown S, Chillingworth T, Churcher C, Collins M, Connor R, Cronin A, Davis P, Feltwell T, Fraser A, Gentles S, Goble A, Hamlin N, Harris D, Hidalgo J, Hodgson G, Holroyd S, et al: The genome sequence of Schizosaccharomyces pombe. Nature. 2002, 415: 871-880. 10.1038/nature724." href="/articles/10.1186/gb-2011-12-7-226#ref-CR1" id="ref-link-section-d86216623e348">1</a>]. Whereas yeast and other fungal species have a single Atg8 gene, multicellular animals, green plants and some protists have several. Animal Atg8 proteins comprise three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3, hereafter referred to as LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16) (Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig1">1a</a>). Humans have a single GATE-16 gene, two GABARAP genes and four LC3 genes (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/gb-2011-12-7-226#Tab1">1</a>). In addition, <i>LC3A</i> encodes two isoforms resulting from alternative splicing. All three subfamilies are also present in diverse other bilateral species and in the earlier diverging animals - cnidarians (such as sea anemones, corals and hydras) and sponges. Atg8 genes have been both duplicated and lost during evolution, leading to the extinction and expansion of some subfamilies in specific lineages (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/gb-2011-12-7-226#Tab2">2</a>). One example is in arthropods: the blacklegged tick <i>Ixodes scapularis</i> (an arachnid) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="VectorBase: I. scapularis. [
 http://iscapularis.vectorbase.org/
 
 ]" href="/articles/10.1186/gb-2011-12-7-226#ref-CR2" id="ref-link-section-d86216623e367">2</a>] has GATE-16, GABARAP and LC3 genes, but in insects, the honey bee <i>Apis mellifera</i> has only a GABARAP and an LC3 gene [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Insights into social insects from the genome of the honeybee Apis mellifera. Nature. 2006, 443: 931-949. 10.1038/nature05260." href="/articles/10.1186/gb-2011-12-7-226#ref-CR3" id="ref-link-section-d86216623e373">3</a>] and the fruit fly <i>Drosophila</i> has two GABARAP genes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="A Database of Drosophila Genes & Genomes. [
 http://flybase.org/
 
 ]" href="/articles/10.1186/gb-2011-12-7-226#ref-CR4" id="ref-link-section-d86216623e379">4</a>]. One of the fruit fly GABARAP genes has no coding region introns and could be the result of a retrotransposition of the other gene's transcript during the emergence of the fruit flies. The human LC3 gene <i>MAP1LC3B2</i> also lacks coding region introns and its coding region has 376 out of 378 bases identical with the human gene <i>MAP1LC3B</i>, which has three coding region introns and is more than 10 kb long (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/articles/10.1186/gb-2011-12-7-226#Tab1">1</a>). The human genome also includes intron-less copies of all three ATG8 gene subfamilies, which are apparently inactive as a result of frameshifts and nonsense mutations.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-1" data-title="Figure 1"><figure><figcaption><b id="Fig1" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 1</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/1" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig1_HTML.jpg?as=webp"><img aria-describedby="Fig1" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig1_HTML.jpg" alt="figure 1" loading="lazy"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-1-desc"><p><b>Evolution and sequence features of Atg8 genes</b>. <b>(a)</b> Atg8 genes in fungi, animals and intermediate-branching species. A schematic tree, based on a sequence-derived phylogenetic tree, showing the three animal Atg8 subfamilies and their presence in key lineages. The subfamilies appear only in animals. Branching between animals and fungi are Atg8 proteins from the few known unicellular species that diverged after the emergence of fungi and before the emergence of multicellular animals. Shown here are Atg8 proteins from the choanoflagellate <i>Monosiga brevicollis</i> (Mbe) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nichols S, Richter DJ, Salamov A, Sequencing JG, Bork P, Lim WA, Manning G, et al: The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature. 2008, 451: 783-788. 10.1038/nature06617." href="/articles/10.1186/gb-2011-12-7-226#ref-CR6" id="ref-link-section-d86216623e410">6</a>], the ichthyosporean <i>Sphaeroforma arctica</i> (Sar) and the amoeba <i>Capsaspora owczarzaki</i> (Cow) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 111" title="Ruiz-Trillo I, Roger AJ, Burger G, Gray MW, Lang BF: A phylogenomic investigation into the origin of metazoa. Mol Biol Evol. 2008, 25: 664-672. 10.1093/molbev/msn006." href="/articles/10.1186/gb-2011-12-7-226#ref-CR111" id="ref-link-section-d86216623e420">111</a>]. The scheme is based on a tree calculated from protein multiple alignment of Atg8 proteins from representative species with complete and almost complete genomic data. The alignment included 117 conserved amino acid positions. The tree was calculated using the PhyML program version 2.4.4, with 100 bootstrap replicates, four substitution rate categories, the HKY nucleotide substitution model and program-estimated Ts/Tv ratios, gamma shape parameters and invariant proportions as previously described [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 112" title="Salzberg Y, Eldar T, Karminsky OD, Itach SB, Pietrokovski S, Don J: Meig1 deficiency causes a severe defect in mouse spermatogenesis. Dev Biol. 2010, 338: 158-167. 10.1016/j.ydbio.2009.11.028." href="/articles/10.1186/gb-2011-12-7-226#ref-CR112" id="ref-link-section-d86216623e423">112</a>]. The subfamily clusters are supported by bootstrap values ranging from 37/100 to 95/100 and also appeared with significant bootstrap values in other trees similarly calculated with different sets of Atg8 genes. The representative species for this scheme were: human, <i>Danio rerio, Xenopus tropicalis, Branchiostoma floridae, Ciona savignyi, Oikopleura dioica, Strongylocentrotus purpuratus, Aplysia californica, Schistosoma mansoni, Schmidtea mediterranea, Drosophila melanogaster, Caenorhabditis elegans, Capitella teleta, Nematostella vectensis, Trichoplax adhaerens, Amphimedon queenslandica, Monosiga brevicollis, Sphaeroforma arctica, Capsaspora owczarzaki, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Allomyces macrogynus</i>, and <i>Tuber melanosporum</i>. <b>(b)</b> Atg8 subfamily sequence features. Sequence logos [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 113" title="Schneider TD, Stephens RM: Sequence logos: a new way to display consensus sequences. Nucleic Acids Res. 1990, 18: 6097-6100. 10.1093/nar/18.20.6097." href="/articles/10.1186/gb-2011-12-7-226#ref-CR113" id="ref-link-section-d86216623e435">113</a>] show the conservation (overall height) and residue prevalence of multiple alignment positions. The alignment includes the core conserved sequence regions, only excluding short non-conserved distal regions of some sequences. The subfamilies are numbered by the coordinates of the human GATE-16, GABARAP and LC3 proteins. Plus signs indicate similar positions between alignments of the GATE-16 and GABARAP subfamilies and between the GABARAP and LC3 subfamilies. Each of the three families is very well conserved across its entire length (apart from the few amino-terminal residues in LC3). The three families are also very similar to each other in most of their positions. The few positions that are only conserved in each family and different between the subfamilies may account for some of the functional differences between the subfamilies. The alignments and logos were constructed as previously described [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 112" title="Salzberg Y, Eldar T, Karminsky OD, Itach SB, Pietrokovski S, Don J: Meig1 deficiency causes a severe defect in mouse spermatogenesis. Dev Biol. 2010, 338: 158-167. 10.1016/j.ydbio.2009.11.028." href="/articles/10.1186/gb-2011-12-7-226#ref-CR112" id="ref-link-section-d86216623e439">112</a>], taking into account sequence redundancy and expected amino acid frequencies. Sequences for the alignments were taken from the CDD [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 114" title="Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH: CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 2011, 39: D225-D229. 10.1093/nar/gkq1189." href="/articles/10.1186/gb-2011-12-7-226#ref-CR114" id="ref-link-section-d86216623e442">114</a>] and PFAM [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 115" title="Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A: The Pfam protein families database. Nucleic Acids Res. 2010, 38: D211-D222. 10.1093/nar/gkp985." href="/articles/10.1186/gb-2011-12-7-226#ref-CR115" id="ref-link-section-d86216623e445">115</a>] database entries cd01611 and PF02991, respectively, and sequences similar to ones in these entries, from protein sequences and translated genomic and EST sequences found in public sequence databases.</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/1" data-track-dest="link:Figure1 Full size image" aria-label="Full size image figure 1" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-1"><figure><figcaption class="c-article-table__figcaption"><b id="Tab1" data-test="table-caption">Table 1 Human ATG8 genes</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/articles/10.1186/gb-2011-12-7-226/tables/1" aria-label="Full size table 1"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-2"><figure><figcaption class="c-article-table__figcaption"><b id="Tab2" data-test="table-caption">Table 2 Atg8 subfamilies in metazoan lineages</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/articles/10.1186/gb-2011-12-7-226/tables/2" aria-label="Full size table 2"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Each Atg8 subfamily has some distinct sequence features (Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig1">1b</a>). For example, position 18 of the GATE-16 subfamily is typically a serine and sometimes an alanine residue. The corresponding position in the GABARAP subfamily, 18, is an invariant glycine residue, and in the LC3 subfamily the corresponding position, 20, is typically hydrophobic (a valine or alanine residue), and only sometimes a serine residue. Positions 40 in GABARAP and 42 in LC3 subfamilies are conserved and typically basic, whereas the GATE-16 family position corresponding to them, 40, is not well conserved and includes basic residues only in some proteins. At present it is unclear what functions, if any, are associated with these sequence features. Sponges, the oldest surviving basal multicellular animals [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Srivastava M, Simakov O, Chapman J, Fahey B, Gauthier ME, Mitros T, Richards GS, Conaco C, Dacre M, Hellsten U, Larroux C, Putnam NH, Stanke M, Adamska M, Darling A, Degnan SM, Oakley TH, Plachetzki DC, Zhai Y, Adamski M, Calcino A, Cummins SF, Goodstein DM, Harris C, Jackson DJ, Leys SP, Shu S, Woodcroft BJ, Vervoort M, Kosik KS, et al: The Amphimedon queenslandica genome and the evolution of animal complexity. Nature. 2010, 466: 720-726. 10.1038/nature09201." href="/articles/10.1186/gb-2011-12-7-226#ref-CR5" id="ref-link-section-d86216623e1227">5</a>], have genes from all three ATG8 subfamilies. Choanoflagellates, unicellular species that are the closest known relatives of animals [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nichols S, Richter DJ, Salamov A, Sequencing JG, Bork P, Lim WA, Manning G, et al: The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature. 2008, 451: 783-788. 10.1038/nature06617." href="/articles/10.1186/gb-2011-12-7-226#ref-CR6" id="ref-link-section-d86216623e1230">6</a>], have ATG8 genes that do not belong to the three metazoan subfamilies (Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig1">1a</a>). It thus seems that the ATG8 gene family diverged into its three subfamilies during the emergence of multicellular animals, and that although the subfamilies underwent further expansion in some lineages, in other lineages some subfamilies were lost. In higher plants the ATG8 genes have also diverged, with <i>Arabidopsis thaliana</i> including eight such genes that can be grouped into three clusters. Different <i>A. thaliana</i> ATG8 genes showed distinct spatial and temporal expression patterns in different tissues [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 7" title="Sláviková S, Shy G, Yao Y, Glozman R, Levanony H, Pietrokovski S, Elazar Z, Galili G: The autophagy-associated Atg8 gene family operates both under favorable growth conditions and under starvation stresses in Arabidopsis plants. J Exp Bot. 2005, 56: 2839-2849. 10.1093/jxb/eri276." href="/articles/10.1186/gb-2011-12-7-226#ref-CR7" id="ref-link-section-d86216623e1243">7</a>].</p></div></div></section><section data-title="Characteristic structural features"><div class="c-article-section" id="Sec2-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec2">Characteristic structural features</h2><div class="c-article-section__content" id="Sec2-content"><p>The structures of several Atg8 family members have been solved for mammals, yeast, invertebrates and the parasite <i>Trypanosoma brucei</i> [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Coyle JE, Qamar S, Rajashankar KR, Nikolov DB: Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. Neuron. 2002, 33: 63-74. 10.1016/S0896-6273(01)00558-X." href="/articles/10.1186/gb-2011-12-7-226#ref-CR8" id="ref-link-section-d86216623e1257">8</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F: The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells. 2004, 9: 611-618. 10.1111/j.1356-9597.2004.00750.x." href="/articles/10.1186/gb-2011-12-7-226#ref-CR15" id="ref-link-section-d86216623e1260">15</a>]. These studies showed that all Atg8 proteins share a strong structural similarity to ubiquitin, despite the lack of similarity in amino acid sequence. GATE-16, the first Atg8 to be crystallized, contains two amino-terminal α-helices in addition to its carboxy-terminal ubiquitin core [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Paz Y, Elazar Z, Fass D: Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p. J Biol Chem. 2000, 275: 25445-25450. 10.1074/jbc.C000307200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR13" id="ref-link-section-d86216623e1263">13</a>]. Subsequent studies confirmed that these features are a unique characteristic of all Atg8 proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Coyle JE, Qamar S, Rajashankar KR, Nikolov DB: Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. Neuron. 2002, 33: 63-74. 10.1016/S0896-6273(01)00558-X." href="/articles/10.1186/gb-2011-12-7-226#ref-CR8" id="ref-link-section-d86216623e1266">8</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F: The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells. 2004, 9: 611-618. 10.1111/j.1356-9597.2004.00750.x." href="/articles/10.1186/gb-2011-12-7-226#ref-CR15" id="ref-link-section-d86216623e1270">15</a>] (Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig2">2</a>). The two amino-terminal α helices differ between the various mammalian Atg8 proteins; thus, for example, the first α helix of the LC3 subfamily is strongly basic, whereas in the GABARAP and GATE-16 subfamilies this region is acidic [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F: The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8. Genes Cells. 2004, 9: 611-618. 10.1111/j.1356-9597.2004.00750.x." href="/articles/10.1186/gb-2011-12-7-226#ref-CR15" id="ref-link-section-d86216623e1276">15</a>]. The ubiquitin core of the Atg8 proteins consists of a four-stranded central β sheet, in which the two central strands are parallel to each other and the two outer strands are antiparallel to the central strands. Between these strands lie two α helices: α3 between β2 and β3, and α4 between β3 and β4 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 16" title="Noda NN, Ohsumi Y, Inagaki F: ATG systems from the protein structural point of view. Chem Rev. 2009, 109: 1587-1598. 10.1021/cr800459r." href="/articles/10.1186/gb-2011-12-7-226#ref-CR16" id="ref-link-section-d86216623e1279">16</a>]. This domain contains a basic feature that is conserved among family members and is suggested to have a role in protein-protein interactions. The molecular surface lying on the opposite side of the three-dimensional structure is poorly conserved and might mediate interactions specific to different Atg8 proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 17" title="Bavro VN, Sola M, Bracher A, Kneussel M, Betz H, Weissenhorn W: Crystal structure of the GABA(A)-receptor-associated protein, GABARAP. EMBO Rep. 2002, 3: 183-189. 10.1093/embo-reports/kvf026." href="/articles/10.1186/gb-2011-12-7-226#ref-CR17" id="ref-link-section-d86216623e1282">17</a>], whereas the conserved domain is probably responsible for characteristic interactions of Atg8 proteins, such as binding to the conjugation machinery proteins.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-2" data-title="Figure 2"><figure><figcaption><b id="Fig2" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 2</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/2" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig2_HTML.jpg?as=webp"><img aria-describedby="Fig2" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig2_HTML.jpg" alt="figure 2" loading="lazy"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-2-desc"><p><b>Crystal structures of the Atg8 family members and ubiquitin</b>. All Atg8s share a similar ubiquitin-like fold with two additional amino-terminal α helices. GATE-16 is shown in blue (Protein Data Bank (PDB): 1EO6), GABARAP in green (PDB: 1KOT), LC3B in red (PDB: 1V49) and ubiquitin in gray (PDB: 1UBI). Helix shape represents an α helix; arrow shape represents a β sheet; arrowhead represents the carboxyl termini of β sheets.</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/2" data-track-dest="link:Figure2 Full size image" aria-label="Full size image figure 2" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>During the autophagic process Atg8 proteins bind to numerous factors, such as proteins and possibly membranes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1308">18</a>]. A study by Coyle <i>et al</i>. [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Coyle JE, Qamar S, Rajashankar KR, Nikolov DB: Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. Neuron. 2002, 33: 63-74. 10.1016/S0896-6273(01)00558-X." href="/articles/10.1186/gb-2011-12-7-226#ref-CR8" id="ref-link-section-d86216623e1314">8</a>] provides structural evidence for conformational changes resulting from protein-protein interactions. GABARAP was found to have two distinct conformations: a closed conformation, in which the α helices project down towards the surface of the ubiquitin core, and an open conformation, in which the ten amino-terminal amino acids are directed away from the ubiquitin core. The latter conformation is stabilized by the oligomeric state of the protein and points to flexibility in the Atg8 amino-terminal region. A conformational change was also reported in an <i>in vitro</i> reconstitution assay of yeast Atg8, in which accessibility of the amino terminus to antibody increased on conjugation of Atg8 to phosphatidylethanolamine (PE)-containing liposomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 19" title="Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y: In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J Biol Chem. 2004, 279: 40584-40592. 10.1074/jbc.M405860200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR19" id="ref-link-section-d86216623e1320">19</a>]. Taken together, these findings suggest that the Atg8 amino-terminal region has a crucial role in the functions of these proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Nakatogawa H, Ichimura Y, Ohsumi Y: Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell. 2007, 130: 165-178. 10.1016/j.cell.2007.05.021." href="/articles/10.1186/gb-2011-12-7-226#ref-CR20" id="ref-link-section-d86216623e1324">20</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z: LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011, 20: 444-454. 10.1016/j.devcel.2011.02.006." href="/articles/10.1186/gb-2011-12-7-226#ref-CR22" id="ref-link-section-d86216623e1327">22</a>]. Differences between the various Atg8 proteins in this region might reflect their distinct functions. The amino-terminal region might also be a target for post-translational regulation.</p></div></div></section><section data-title="Localization and function"><div class="c-article-section" id="Sec3-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec3">Localization and function</h2><div class="c-article-section__content" id="Sec3-content"><h3 class="c-article__sub-heading" id="Sec4">Gene expression</h3><p>Atg8 proteins seem to be ubiquitously expressed, although some subfamily members are expressed at increased levels in certain tissues. The signaling pathways and transcription factors regulating their expression are only partially characterized. Of the LC3 subfamily, <i>LC3C</i>, which is transcribed at lower levels than other members of this subfamily, is expressed predominantly in the lung [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 23" title="He H, Dang Y, Dai F, Guo Z, Wu J, She X, Pei Y, Chen Y, Ling W, Wu C, Zhao S, Liu JO, Yu L: Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B. J Biol Chem. 2003, 278: 29278-29287. 10.1074/jbc.M303800200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR23" id="ref-link-section-d86216623e1345">23</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 24" title="Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S: Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein. Genomics. 2001, 74: 408-413. 10.1006/geno.2001.6555." href="/articles/10.1186/gb-2011-12-7-226#ref-CR24" id="ref-link-section-d86216623e1348">24</a>]. Expression analysis of the different GABARAP proteins reveals a distinct pattern: GABARAP-L1 is expressed predominantly in the central nervous system, similar to GATE-16, which is strongly expressed in the brain, whereas the expression of GABARAP is more marked in the endocrine glands [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Nemos C, Mansuy V, Vernier-Magnin S, Fraichard A, Jouvenot M, Delage-Mourroux R: Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system. Brain Res Mol Brain Res. 2003, 119: 216-219." href="/articles/10.1186/gb-2011-12-7-226#ref-CR25" id="ref-link-section-d86216623e1351">25</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 26" title="Sagiv Y, Legesse-Miller A, Porat A, Elazar Z: GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J. 2000, 19: 1494-1504. 10.1093/emboj/19.7.1494." href="/articles/10.1186/gb-2011-12-7-226#ref-CR26" id="ref-link-section-d86216623e1354">26</a>].</p><p>Upregulation of Atg8s is observed under various stress conditions [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 27" title="Egami Y, Kiryu-Seo S, Yoshimori T, Kiyama H: Induced expressions of Rab24 GTPase and LC3 in nerve-injured motor neurons. Biochem Biophys Res Commun. 2005, 337: 1206-1213. 10.1016/j.bbrc.2005.09.171." href="/articles/10.1186/gb-2011-12-7-226#ref-CR27" id="ref-link-section-d86216623e1360">27</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 30" title="van Zutphen T, Baerends RJ, Susanna KA, de Jong A, Kuipers OP, Veenhuis M, van der Klei IJ: Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis. BMC Genomics. 2010, 11: 1-10.1186/1471-2164-11-1." href="/articles/10.1186/gb-2011-12-7-226#ref-CR30" id="ref-link-section-d86216623e1363">30</a>]. Although the transcriptional regulation of Atg8 genes is largely unknown, several reports have shown that the transcription factors FoxO1, FoxO3 and E2F1 regulate Atg8s in this process in mammalian cells [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 31" title="Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M: FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007, 6: 458-471. 10.1016/j.cmet.2007.11.001." href="/articles/10.1186/gb-2011-12-7-226#ref-CR31" id="ref-link-section-d86216623e1366">31</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 34" title="Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, Lecker SH, Goldberg AL: FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007, 6: 472-483. 10.1016/j.cmet.2007.11.004." href="/articles/10.1186/gb-2011-12-7-226#ref-CR34" id="ref-link-section-d86216623e1369">34</a>]. Deciphering the expression patterns of specific Atg8 genes at transcriptional and translational levels may shed new light on their different physiological roles.</p><h3 class="c-article__sub-heading" id="Sec5">The role of Atg8 in intracellular trafficking processes</h3><p>Atg8s were originally implicated in membrane trafficking processes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 35" title="Elazar Z, Scherz-Shouval R, Shorer H: Involvement of LMA1 and GATE-16 family members in intracellular membrane dynamics. Biochim Biophys Acta. 2003, 1641: 145-156. 10.1016/S0167-4889(03)00086-7." href="/articles/10.1186/gb-2011-12-7-226#ref-CR35" id="ref-link-section-d86216623e1380">35</a>]. Members of this protein family were initially connected to the SNARE fusion machinery that mediates the vast majority of intracellular trafficking processes. The AAA ATPase N-ethylmaleimide sensitive factor (NSF) promotes the disassembly of the SNARE complex, a step essential for multiple membrane fusion events. GATE-16 was characterized as a factor essential for intra-Golgi protein transport and was later shown to modulate this process by coupling NSF activity and the Golgi SNARE factor GOS-28 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 26" title="Sagiv Y, Legesse-Miller A, Porat A, Elazar Z: GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J. 2000, 19: 1494-1504. 10.1093/emboj/19.7.1494." href="/articles/10.1186/gb-2011-12-7-226#ref-CR26" id="ref-link-section-d86216623e1383">26</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 36" title="Legesse-Miller A, Sagiv Y, Porat A, Elazar Z: Isolation and characterization of a novel low molecular weight protein involved in intra-Golgi traffic. J Biol Chem. 1998, 273: 3105-3109. 10.1074/jbc.273.5.3105." href="/articles/10.1186/gb-2011-12-7-226#ref-CR36" id="ref-link-section-d86216623e1386">36</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 37" title="Muller JM, Shorter J, Newman R, Deinhardt K, Sagiv Y, Elazar Z, Warren G, Shima DT: Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion. J Cell Biol. 2002, 157: 1161-1173. 10.1083/jcb.200202082." href="/articles/10.1186/gb-2011-12-7-226#ref-CR37" id="ref-link-section-d86216623e1389">37</a>]. LC3 was first characterized as a protein that co-purified with microtubule-associated proteins 1A and 1B [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 38" title="Kuznetsov SA, Gelfand VI: 18 kDa microtubule-associated protein: identification as a new light chain (LC-3) of microtubule-associated protein 1 (MAP-1). FEBS Lett. 1987, 212: 145-148. 10.1016/0014-5793(87)81574-0." href="/articles/10.1186/gb-2011-12-7-226#ref-CR38" id="ref-link-section-d86216623e1392">38</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 39" title="Mann SS, Hammarback JA: Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B. J Biol Chem. 1994, 269: 11492-11497." href="/articles/10.1186/gb-2011-12-7-226#ref-CR39" id="ref-link-section-d86216623e1396">39</a>], but no direct involvement of this protein in membrane trafficking processes has been reported. GABARAP, however, was identified as a cytosolic protein that is localized to transport vesicles, the Golgi network and the endoplasmic reticulum (ER) and that interacts with the γ2 subunit of GABA(A) receptors [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 40" title="Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW: GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature. 1999, 397: 69-72. 10.1038/16264." href="/articles/10.1186/gb-2011-12-7-226#ref-CR40" id="ref-link-section-d86216623e1399">40</a>]. This interaction is thought to be essential for trafficking of the GABA(A) receptor to the plasma membrane [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 41" title="Leil TA, Chen ZW, Chang CS, Olsen RW: GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons. J Neurosci. 2004, 24: 11429-11438. 10.1523/JNEUROSCI.3355-04.2004." href="/articles/10.1186/gb-2011-12-7-226#ref-CR41" id="ref-link-section-d86216623e1402">41</a>]. A recent study showed that GABA(A) receptor trafficking is dependent on processing of the GABARAP carboxyl terminus [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 42" title="Chen ZW, Chang CS, Leil TA, Olsen RW: C-terminal modification is required for GABARAP-mediated GABA(A) receptor trafficking. J Neurosci. 2007, 27: 6655-6663. 10.1523/JNEUROSCI.0919-07.2007." href="/articles/10.1186/gb-2011-12-7-226#ref-CR42" id="ref-link-section-d86216623e1405">42</a>]. GABARAP's involvement in vesicle transport is not limited to the GABA(A) receptor; other plasma membrane proteins, such as the transferrin receptor, interact with GABARAP, although the role of GABARAP in their transport is not well established [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 43" title="Green F, O'Hare T, Blackwell A, Enns CA: Association of human transferrin receptor with GABARAP. FEBS Lett. 2002, 518: 101-106. 10.1016/S0014-5793(02)02655-8." href="/articles/10.1186/gb-2011-12-7-226#ref-CR43" id="ref-link-section-d86216623e1408">43</a>]. Moreover, ER-to-Golgi transport is also controlled by GABARAP, as it interacts with PX-RICS, which is involved in transport of synaptic proteins to the ER. It has been suggested that these factors mediate the transport of the transmembrane protein N-cadherin and its receptor β-catenin from the ER, thus controlling cell-cell adhesion [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 44" title="Nakamura T, Hayashi T, Nasu-Nishimura Y, Sakaue F, Morishita Y, Okabe T, Ohwada S, Matsuura K, Akiyama T: PX-RICS mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex. Genes Dev. 2008, 22: 1244-1256. 10.1101/gad.1632308." href="/articles/10.1186/gb-2011-12-7-226#ref-CR44" id="ref-link-section-d86216623e1411">44</a>]. The role of GABARAP in intracellular transport is also supported by its interaction with NSF, a component essential for SNARE-mediated fusion [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 41" title="Leil TA, Chen ZW, Chang CS, Olsen RW: GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons. J Neurosci. 2004, 24: 11429-11438. 10.1523/JNEUROSCI.3355-04.2004." href="/articles/10.1186/gb-2011-12-7-226#ref-CR41" id="ref-link-section-d86216623e1415">41</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 45" title="Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ: The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Mol Cell Neurosci. 2001, 18: 13-25. 10.1006/mcne.2001.1005." href="/articles/10.1186/gb-2011-12-7-226#ref-CR45" id="ref-link-section-d86216623e1418">45</a>]. Similar to LC3, GABARAP binds to tubulin through its amino-terminal region, an interaction that regulates clustering of GABA(A) receptors [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Coyle JE, Qamar S, Rajashankar KR, Nikolov DB: Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. Neuron. 2002, 33: 63-74. 10.1016/S0896-6273(01)00558-X." href="/articles/10.1186/gb-2011-12-7-226#ref-CR8" id="ref-link-section-d86216623e1421">8</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 46" title="Chen L, Wang H, Vicini S, Olsen RW: The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics. Proc Natl Acad Sci USA. 2000, 97: 11557-11562." href="/articles/10.1186/gb-2011-12-7-226#ref-CR46" id="ref-link-section-d86216623e1424">46</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 47" title="Wang H, Olsen RW: Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction. J Neurochem. 2000, 75: 644-655." href="/articles/10.1186/gb-2011-12-7-226#ref-CR47" id="ref-link-section-d86216623e1427">47</a>].</p><p>Like GABARAP, GABARAP-L1 has been shown to interact with the GABA(A) receptor and tubulin in brain extracts, as well as with NSF [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 48" title="Chen C, Li JG, Chen Y, Huang P, Wang Y, Liu-Chen LY: GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor. J Biol Chem. 2006, 281: 7983-7993. 10.1074/jbc.M509805200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR48" id="ref-link-section-d86216623e1433">48</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 49" title="Mansuy V, Boireau W, Fraichard A, Schlick JL, Jouvenot M, Delage-Mourroux R: GEC1, a protein related to GABARAP, interacts with tubulin and GABA(A) receptor. Biochem Biophys Res Commun. 2004, 325: 639-648. 10.1016/j.bbrc.2004.10.072." href="/articles/10.1186/gb-2011-12-7-226#ref-CR49" id="ref-link-section-d86216623e1436">49</a>]. GABARAP-L1 also binds directly to the G-protein-coupled κ-opioid receptor and mediates its transport in a manner dependent on modification of the carboxyl terminus [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 48" title="Chen C, Li JG, Chen Y, Huang P, Wang Y, Liu-Chen LY: GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor. J Biol Chem. 2006, 281: 7983-7993. 10.1074/jbc.M509805200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR48" id="ref-link-section-d86216623e1439">48</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 50" title="Chen C, Wang Y, Huang P, Liu-Chen LY: Effects of C-terminal modifications of GEC1 Protein and {gamma}-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP), two microtubule-associated proteins, on {kappa} opioid receptor expression. J Biol Chem. 2011, 286: 15106-15115. 10.1074/jbc.M111.230896." href="/articles/10.1186/gb-2011-12-7-226#ref-CR50" id="ref-link-section-d86216623e1442">50</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 51" title="Chen Y, Chen C, Kotsikorou E, Lynch DL, Reggio PH, Liu-Chen LY: GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect. J Biol Chem. 2009, 284: 1673-1685." href="/articles/10.1186/gb-2011-12-7-226#ref-CR51" id="ref-link-section-d86216623e1445">51</a>]. The role of mammalian Atg8s in intracellular trafficking processes is depicted in Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig3">3</a>.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-3" data-title="Figure 3"><figure><figcaption><b id="Fig3" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 3</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/3" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig3_HTML.jpg?as=webp"><img aria-describedby="Fig3" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig3_HTML.jpg" alt="figure 3" loading="lazy"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-3-desc"><p><b>Role of Atg8 proteins in intracellular trafficking processes</b>. <b>(a)</b> The GABARAP subfamily members GABARAP (GB) and GABARAP-L1 (GB1) participate in the transport of plasma membrane proteins, such as the GABA(A), κ-opioid and transferrin receptors, from the Golgi to the plasma membrane (PM). <b>(b)</b> The GABARAP and the GATE-16 subfamilies both participate in transport from the ER to the Golgi and within the Golgi apparatus. GABARAP, together with PX-RICS, participates in N-cadherin/β-catenin transport from the ER to the Golgi. GATE-16 has been implicated in intra-Golgi transport through its interaction with Golgi SNARE protein 28 (GOS-28). Both subfamilies can interact with NSF, suggesting that they participate in regulation of membrane fusion events.</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/3" data-track-dest="link:Figure3 Full size image" aria-label="Full size image figure 3" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Consistent with the involvement of mammalian Atg8s in membrane fusion events, the yeast <i>Pichia pastoris</i> Atg8 was recently found to mediate vacuolar fusion during adaptation from glucose- to methanol-containing medium [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 52" title="Tamura N, Oku M, Sakai Y: Atg8 regulates vacuolar membrane dynamics in a lipidation-independent manner in Pichia pastoris. J Cell Sci. 2010, 123: 4107-4116. 10.1242/jcs.070045." href="/articles/10.1186/gb-2011-12-7-226#ref-CR52" id="ref-link-section-d86216623e1484">52</a>]. This activity might involve the previously reported interaction of Atg8 with SNAREs in the yeast system [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 53" title="Legesse-Miller A, Sagiv Y, Glozman R, Elazar Z: Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. J Biol Chem. 2000, 275: 32966-32973." href="/articles/10.1186/gb-2011-12-7-226#ref-CR53" id="ref-link-section-d86216623e1487">53</a>].</p><p>To summarize, the mammalian GABARAP and GATE-16 subfamilies and the yeast Atg8 have been implicated in intracellular protein trafficking, but their exact role in these processes is not fully understood. The current consensus suggests that these molecules mediate trafficking both by escorting individual cargo molecules and possibly as regulators of membrane fusion events.</p><h3 class="c-article__sub-heading" id="Sec6">Atg8 proteins are key cytoplasm-to-vacuole targeting and autophagic factors</h3><p>The first link between Atg8 proteins and autophagy was established in <i>Saccharomyces cerevisiae</i>, where the single Atg8 protein was identified as an autophagy and cytoplasm-to-vacuole targeting essential factor [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 54" title="Harding TM, Morano KA, Scott SV, Klionsky DJ: Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995, 131: 591-602. 10.1083/jcb.131.3.591." href="/articles/10.1186/gb-2011-12-7-226#ref-CR54" id="ref-link-section-d86216623e1503">54</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 56" title="Scott SV, Hefner-Gravink A, Morano KA, Noda T, Ohsumi Y, Klionsky DJ: Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole. Proc Natl Acad Sci USA. 1996, 93: 12304-12308. 10.1073/pnas.93.22.12304." href="/articles/10.1186/gb-2011-12-7-226#ref-CR56" id="ref-link-section-d86216623e1506">56</a>]. Cytoplasm-to-vacuole targeting is responsible for transporting vacuolar protein residents, such as aminopeptidase I (Ape1) and α-mannosidase (Ams1), to the vacuole [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 57" title="Lynch-Day MA, Klionsky DJ: The Cvt pathway as a model for selective autophagy. FEBS Lett. 2010, 584: 1359-1366. 10.1016/j.febslet.2010.02.013." href="/articles/10.1186/gb-2011-12-7-226#ref-CR57" id="ref-link-section-d86216623e1509">57</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 58" title="Suzuki K, Kondo C, Morimoto M, Ohsumi Y: Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p. J Biol Chem. 2010, 285: 30019-30025. 10.1074/jbc.M110.143511." href="/articles/10.1186/gb-2011-12-7-226#ref-CR58" id="ref-link-section-d86216623e1512">58</a>]. In yeast, Atg8 expression is upregulated during nitrogen starvation and is degraded in the vacuole following recruitment into autophagosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 59" title="Huang WP, Scott SV, Kim J, Klionsky DJ: The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 2000, 275: 5845-5851. 10.1074/jbc.275.8.5845." href="/articles/10.1186/gb-2011-12-7-226#ref-CR59" id="ref-link-section-d86216623e1516">59</a>]. Subsequent to its translation, Atg8 undergoes several modifications, starting with cleavage in its carboxy-terminal region to expose a glycine residue. This cleavage is mediated by the cysteine protease Atg4, which is specific to Atg8 proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 60" title="Kim J, Huang WP, Klionsky DJ: Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001, 152: 51-64. 10.1083/jcb.152.1.51." href="/articles/10.1186/gb-2011-12-7-226#ref-CR60" id="ref-link-section-d86216623e1519">60</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 61" title="Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, Ohsumi Y: The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 2000, 151: 263-276. 10.1083/jcb.151.2.263." href="/articles/10.1186/gb-2011-12-7-226#ref-CR61" id="ref-link-section-d86216623e1522">61</a>]. The cleaved Atg8 is than processed by a ubiquitin-like conjugation machinery composed of Atg7, an E1-like enzyme [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 62" title="Tanida I, Mizushima N, Kiyooka M, Ohsumi M, Ueno T, Ohsumi Y, Kominami E: Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy. Mol Biol Cell. 1999, 10: 1367-1379." href="/articles/10.1186/gb-2011-12-7-226#ref-CR62" id="ref-link-section-d86216623e1525">62</a>], and Atg3, a specific E2-like ligase [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 63" title="Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M: AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae. J Bacteriol. 1997, 179: 1068-1076." href="/articles/10.1186/gb-2011-12-7-226#ref-CR63" id="ref-link-section-d86216623e1528">63</a>]. Unlike ubiquitin, which is conjugated to a protein, Atg8 is covalently conjugated to PE lipid through its carboxy-terminal exposed glycine [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 64" title="Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y: A ubiquitin-like system mediates protein lipidation. Nature. 2000, 408: 488-492. 10.1038/35044114." href="/articles/10.1186/gb-2011-12-7-226#ref-CR64" id="ref-link-section-d86216623e1531">64</a>]. Atg4 has a dual role, as it is also responsible for the de-conjugation of Atg8 from the autophagic membrane (Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig4">4a</a>) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 64" title="Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y: A ubiquitin-like system mediates protein lipidation. Nature. 2000, 408: 488-492. 10.1038/35044114." href="/articles/10.1186/gb-2011-12-7-226#ref-CR64" id="ref-link-section-d86216623e1538">64</a>]. Similar to many other cytoplasm-to-vacuole targeting and autophagic factors, Atg8 is localized to the pre-autophagosomal structure under basal and nitrogen depletion conditions [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 65" title="Suzuki K, Ohsumi Y: Current knowledge of the pre-autophagosomal structure (PAS). FEBS Lett. 2010, 584: 1280-1286. 10.1016/j.febslet.2010.02.001." href="/articles/10.1186/gb-2011-12-7-226#ref-CR65" id="ref-link-section-d86216623e1541">65</a>], a process dependent on the phagophore resident complex Atg5-Atg12-Atg16 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 66" title="Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y: The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001, 20: 5971-5981. 10.1093/emboj/20.21.5971." href="/articles/10.1186/gb-2011-12-7-226#ref-CR66" id="ref-link-section-d86216623e1544">66</a>]. The Atg5-Atg12 conjugate acts as an E3-like ligase, mediating the formation of Atg8-PE conjugate <i>in vitro</i>, suggesting a role for this complex in determining the Atg8 conjugation site in cells [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 67" title="Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F, Ohsumi Y: The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem. 2007, 282: 37298-37302. 10.1074/jbc.C700195200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR67" id="ref-link-section-d86216623e1550">67</a>]. Recent evidence implicates Atg8 in both autophagic cargo recruitment and autophagosome biogenesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1554">18</a>]. Atg8 has a key role in the cytoplasm-to-vacuole targeting pathway as it binds to the receptors Atg19 and Atg34, thereby mediating the recruitment of different cargo molecules into autophagosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 57" title="Lynch-Day MA, Klionsky DJ: The Cvt pathway as a model for selective autophagy. FEBS Lett. 2010, 584: 1359-1366. 10.1016/j.febslet.2010.02.013." href="/articles/10.1186/gb-2011-12-7-226#ref-CR57" id="ref-link-section-d86216623e1557">57</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 58" title="Suzuki K, Kondo C, Morimoto M, Ohsumi Y: Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p. J Biol Chem. 2010, 285: 30019-30025. 10.1074/jbc.M110.143511." href="/articles/10.1186/gb-2011-12-7-226#ref-CR58" id="ref-link-section-d86216623e1560">58</a>]. Atg8 also participates in formation of the autophagosome and is essential for elongation of the autophagic membrane [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 68" title="Abeliovich H, Dunn WA, Kim J, Klionsky DJ: Dissection of autophagosome biogenesis into distinct nucleation and expansion steps. J Cell Biol. 2000, 151: 1025-1034. 10.1083/jcb.151.5.1025." href="/articles/10.1186/gb-2011-12-7-226#ref-CR68" id="ref-link-section-d86216623e1563">68</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 69" title="Xie Z, Nair U, Klionsky DJ: Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell. 2008, 19: 3290-3298. 10.1091/mbc.E07-12-1292." href="/articles/10.1186/gb-2011-12-7-226#ref-CR69" id="ref-link-section-d86216623e1566">69</a>]. This role was further established using an <i>in vitro</i> liposome-based system, where it can promote membrane fusion [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Nakatogawa H, Ichimura Y, Ohsumi Y: Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell. 2007, 130: 165-178. 10.1016/j.cell.2007.05.021." href="/articles/10.1186/gb-2011-12-7-226#ref-CR20" id="ref-link-section-d86216623e1573">20</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z: LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011, 20: 444-454. 10.1016/j.devcel.2011.02.006." href="/articles/10.1186/gb-2011-12-7-226#ref-CR22" id="ref-link-section-d86216623e1576">22</a>]. The roles of Atg8 in autophagosome biogenesis and in cargo recruitment overlap, as mutations that abolish Atg8 binding to Atg19 receptor also disrupt autophagosome biogenesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 70" title="Amar N, Lustig G, Ichimura Y, Ohsumi Y, Elazar Z: Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy. EMBO Rep. 2006, 7: 635-642." href="/articles/10.1186/gb-2011-12-7-226#ref-CR70" id="ref-link-section-d86216623e1579">70</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 71" title="Ho KH, Chang HE, Huang WP: Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function. Autophagy. 2009, 5: 461-471. 10.4161/auto.5.4.7696." href="/articles/10.1186/gb-2011-12-7-226#ref-CR71" id="ref-link-section-d86216623e1582">71</a>]. In addition to its interaction with the conjugation proteins, Atg8 also binds to other autophagic factors, such as Atg1, which might regulate its recruitment and activity on the autophagic membrane [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 60" title="Kim J, Huang WP, Klionsky DJ: Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001, 152: 51-64. 10.1083/jcb.152.1.51." href="/articles/10.1186/gb-2011-12-7-226#ref-CR60" id="ref-link-section-d86216623e1585">60</a>]. Other, more general trafficking factors interact with Atg8, including Shp1, a substrate that recruits a cofactor of Cdc48. This interaction was suggested to control the formation of autophagosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 72" title="Krick R, Bremer S, Welter E, Schlotterhose P, Muehe Y, Eskelinen EL, Thumm M: Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J Cell Biol. 2010, 190: 965-973. 10.1083/jcb.201002075." href="/articles/10.1186/gb-2011-12-7-226#ref-CR72" id="ref-link-section-d86216623e1588">72</a>], indicating that Atg8 might provide a link between classical autophagic machinery and general trafficking factors that are crucial for autophagy.</p><div class="c-article-section__figure js-c-reading-companion-figures-item" data-test="figure" data-container-section="figure" id="figure-4" data-title="Figure 4"><figure><figcaption><b id="Fig4" class="c-article-section__figure-caption" data-test="figure-caption-text">Figure 4</b></figcaption><div class="c-article-section__figure-content"><div class="c-article-section__figure-item"><a class="c-article-section__figure-link" data-test="img-link" data-track="click" data-track-label="image" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/4" rel="nofollow"><picture><source type="image/webp" srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig4_HTML.jpg?as=webp"><img aria-describedby="Fig4" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_Article_2554_Fig4_HTML.jpg" alt="figure 4" loading="lazy"></picture></a></div><div class="c-article-section__figure-description" data-test="bottom-caption" id="figure-4-desc"><p><b>Atg8s in autophagy</b>. <b>(a)</b> The conjugation of Atg8 proteins to phosphatidylethanolamine (PE) mediated by a series of steps involving Atg proteins. Following translation, Atg8 proteins are cleaved by the Atg4 protease at the carboxyl terminus to expose a glycine residue. This glycine is then activated by the E1-like enzyme Atg7 and transferred to the E2-like enzyme Atg3. Finally, the conjugation of Atg8 proteins to PE is mediated by the E3-like complex Atg5-Atg12-Atg16. The association of Atg8 proteins with the autophagic membrane is reversible and is mediated by Atg4. <b>(b)</b> The role of Atg8 proteins in the autophagic process. Atg8 proteins are recruited to the autophagic membrane together with autophagic cargo adaptors. On the autophagic membrane Atg8 proteins are conjugated to PE lipids, enabling them to mediate membrane fusion events leading to autophagosome biogenesis. Different Atg8 proteins recruit distinct adaptors and are therefore responsible for the delivery of specific cargo (protein aggregates, organelles such as mitochondria and pathogens) for lysosomal degradation.</p></div></div><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="article-link" data-track="click" data-track-label="button" data-track-action="view figure" href="/articles/10.1186/gb-2011-12-7-226/figures/4" data-track-dest="link:Figure4 Full size image" aria-label="Full size image figure 4" rel="nofollow"><span>Full size image</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Although mammalian Atg8 proteins were originally implicated in intracellular trafficking processes, they are all found within autophagosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 73" title="Chakrama FZ, Seguin-Py S, Le Grand JN, Fraichard A, Delage-Mourroux R, Despouy G, Perez V, Jouvenot M, Boyer-Guittaut M: GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy. 2010" href="/articles/10.1186/gb-2011-12-7-226#ref-CR73" id="ref-link-section-d86216623e1621">73</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 75" title="Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T: LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004, 117: 2805-2812. 10.1242/jcs.01131." href="/articles/10.1186/gb-2011-12-7-226#ref-CR75" id="ref-link-section-d86216623e1624">75</a>]. Collectively, they undergo similar post-translational modifications to those of yeast Atg8, but this is mediated by mammalian orthologs of Atg4, Atg7 and Atg3 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 76" title="Tanida I, Ueno T, Kominami E: LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004, 36: 2503-2518. 10.1016/j.biocel.2004.05.009." href="/articles/10.1186/gb-2011-12-7-226#ref-CR76" id="ref-link-section-d86216623e1627">76</a>]. It was suggested that Atg16L (the mammalian Atg16) determines the lipidation site of LC3 and serves as its E3 ligase [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 77" title="Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T: The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell. 2008, 19: 2092-2100. 10.1091/mbc.E07-12-1257." href="/articles/10.1186/gb-2011-12-7-226#ref-CR77" id="ref-link-section-d86216623e1630">77</a>]. Arrival of Atg8 proteins at the autophagic membrane depends on the hierarchical recruitment of numerous autophagic factors, including phosphatidylinositol-3-phosphate-binding proteins [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1633">18</a>].</p><p>Consistent with the presence of multiple Atg8 members in mammals, Atg4 also seems to have several homologs. These homologs show different specificities toward Atg8 proteins: Atg4B shows a broad spectrum for all family members [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 78" title="Hemelaar J, Lelyveld VS, Kessler BM, Ploegh HL: A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J Biol Chem. 2003, 278: 51841-51850. 10.1074/jbc.M308762200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR78" id="ref-link-section-d86216623e1639">78</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 79" title="Tanida I, Ueno T, Kominami E: Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes. J Biol Chem. 2004, 279: 47704-47710. 10.1074/jbc.M407016200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR79" id="ref-link-section-d86216623e1642">79</a>], whereas Atg4A is specific to the GABARAP and GATE-16 subfamilies [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 80" title="Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM: Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J Biol Chem. 2011, 286: 7327-7338. 10.1074/jbc.M110.199059." href="/articles/10.1186/gb-2011-12-7-226#ref-CR80" id="ref-link-section-d86216623e1645">80</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 81" title="Scherz-Shouval R, Sagiv Y, Shorer H, Elazar Z: The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A. J Biol Chem. 2003, 278: 14053-14058. 10.1074/jbc.M212108200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR81" id="ref-link-section-d86216623e1648">81</a>]. By contrast, Atg4C and Atg4D are less active and their role in the autophagic process has yet to be established [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 80" title="Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM: Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J Biol Chem. 2011, 286: 7327-7338. 10.1074/jbc.M110.199059." href="/articles/10.1186/gb-2011-12-7-226#ref-CR80" id="ref-link-section-d86216623e1651">80</a>]. Atg4 might function in pathways other than autophagy, as cleavage of Atg4D by caspase increases its activity and consequently promotes GABARAP-L1 processing [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 82" title="Betin VM, Lane JD: Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J Cell Sci. 2009, 122: 2554-2566. 10.1242/jcs.046250." href="/articles/10.1186/gb-2011-12-7-226#ref-CR82" id="ref-link-section-d86216623e1655">82</a>]. Atg4 regulates a critical step in the autophagic process and is therefore subjected to regulation by reactive oxygen species, for example, which prevent it from reversing the conjugation of Atg8 proteins to PE during autophagy [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 83" title="Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z: Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007, 26: 1749-1760. 10.1038/sj.emboj.7601623." href="/articles/10.1186/gb-2011-12-7-226#ref-CR83" id="ref-link-section-d86216623e1658">83</a>].</p><p>Among Atg proteins, the Atg8 family is the only one associated with mature autophagosomes and members therefore serve as <i>bona fide</i> markers for this unique organelle. Thus, transgenic mice and tissue-culture cells expressing GFP-LC3 have been used to investigate autophagy [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 84" title="Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y: In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004, 15: 1101-1111." href="/articles/10.1186/gb-2011-12-7-226#ref-CR84" id="ref-link-section-d86216623e1667">84</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 85" title="Tanida I, Waguri S: Measurement of autophagy in cells and tissues. Methods Mol Biol. 2010, 648: 193-214. 10.1007/978-1-60761-756-3_13." href="/articles/10.1186/gb-2011-12-7-226#ref-CR85" id="ref-link-section-d86216623e1670">85</a>]. However, the existence of numerous mammalian Atg8 proteins has hindered investigation of their precise role in autophagy. Several approaches aimed at disrupting the functioning of Atg8 proteins by preventing their conjugation to PE have therefore been used, including the generation of Atg3-null mice and expression of a dominant-negative mutant of the promiscuous protease Atg4B. These have led to the conclusion that PE-conjugated Atg8 proteins are active during autophagosome formation and are essential for the elongation and closure of the initial autophagic membrane, the phagophore [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 86" title="Fujita N, Hayashi-Nishino M, Fukumoto H, Omori H, Yamamoto A, Noda T, Yoshimori T: An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure. Mol Biol Cell. 2008, 19: 4651-4659. 10.1091/mbc.E08-03-0312." href="/articles/10.1186/gb-2011-12-7-226#ref-CR86" id="ref-link-section-d86216623e1673">86</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 88" title="Sou YS, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T, Sawada N, Yamada A, Mizushima N, Uchiyama Y, Kominami E, Tanaka K, Komatsu M: The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell. 2008, 19: 4762-4775. 10.1091/mbc.E08-03-0309." href="/articles/10.1186/gb-2011-12-7-226#ref-CR88" id="ref-link-section-d86216623e1676">88</a>]. A recent report [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z: LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011, 20: 444-454. 10.1016/j.devcel.2011.02.006." href="/articles/10.1186/gb-2011-12-7-226#ref-CR22" id="ref-link-section-d86216623e1680">22</a>] implicates both the LC3 and the GABARAP subfamilies in membrane fusion following conjugation to PE. This study [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z: LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011, 20: 444-454. 10.1016/j.devcel.2011.02.006." href="/articles/10.1186/gb-2011-12-7-226#ref-CR22" id="ref-link-section-d86216623e1683">22</a>] revealed that the first amino-terminal α helix of the Atg8 proteins was both essential and sufficient for this activity. Moreover, different characteristics within the amino termini of the Atg8 subfamilies are involved in their fusion activities. The first attempt to investigate the role of each Atg8 subfamily in autophagosome biogenesis was prompted by a study in which individual Atg8 proteins were knocked down [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 89" title="Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z: LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 2010, 29: 1792-1802. 10.1038/emboj.2010.74." href="/articles/10.1186/gb-2011-12-7-226#ref-CR89" id="ref-link-section-d86216623e1686">89</a>]. Apparently, both the LC3 and the GABARAP/GATE-16 subfamilies are essential for autophagy, as they act at different stages of autophagosome formation: members of the LC3 subfamily are responsible for the elongation of the autophagic membrane, whereas GABARAP/GATE-16 subfamily members act downstream in a step coupled to dissociation of the Atg12-Atg5-Atg16L complex [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 89" title="Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z: LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 2010, 29: 1792-1802. 10.1038/emboj.2010.74." href="/articles/10.1186/gb-2011-12-7-226#ref-CR89" id="ref-link-section-d86216623e1689">89</a>]. In addition to their direct role in fusion events during autophagosome biogenesis, Atg8 proteins have an indirect role in which their binding to diabetes- and obesity-regulated protein (DOR) and to tumor protein 53-induced nuclear protein 1 (TP53INP2), two proteins that shuttle between the nucleus and the cytoplasm, regulates autophagosome biogenesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 90" title="Mauvezin C, Orpinell M, Francis VA, Mansilla F, Duran J, Ribas V, Palacin M, Boya P, Teleman AA, Zorzano A: The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells. EMBO Rep. 2010, 11: 37-44. 10.1038/embor.2009.242." href="/articles/10.1186/gb-2011-12-7-226#ref-CR90" id="ref-link-section-d86216623e1692">90</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 91" title="Nowak J, Archange C, Tardivel-Lacombe J, Pontarotti P, Pebusque MJ, Vaccaro MI, Velasco G, Dagorn JC, Iovanna JL: The TP53INP2 protein is required for autophagy in mammalian cells. Mol Biol Cell. 2009, 20: 870-881." href="/articles/10.1186/gb-2011-12-7-226#ref-CR91" id="ref-link-section-d86216623e1695">91</a>].</p><p>The crucial role of Atg8 proteins in autophagosome biogenesis is controlled by numerous factors and modifications, such as acetylation and phosphorylation. Acetylation of the autophagic factors Atg5, Atg7, Atg8 and Atg12 is mediated by the acetyltransferase p300 and negatively regulates their activity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 92" title="Lee IH, Finkel T: Regulation of autophagy by the p300 acetyltransferase. J Biol Chem. 2009, 284: 6322-6328." href="/articles/10.1186/gb-2011-12-7-226#ref-CR92" id="ref-link-section-d86216623e1702">92</a>]. Phosphorylation of LC3 seems to have a similar effect, as it was recently reported to negatively regulate autophagy [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 93" title="Cherra SJ, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, Day BW, Chu CT: Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol. 2010, 190: 533-539. 10.1083/jcb.201002108." href="/articles/10.1186/gb-2011-12-7-226#ref-CR93" id="ref-link-section-d86216623e1705">93</a>]. Overall, Atg8s serve as key factors in the autophagic process by directly mediating membrane-remodeling processes and interacting with an extensive repertoire of proteins. These features are indispensable for the formation of an intact autophagosome and are therefore tightly regulated.</p><h3 class="c-article__sub-heading" id="Sec7">Atg8 proteins are involved in recruiting cargo into autophagosomes</h3><p>The role of Atg8s in autophagy extends beyond their function in autophagosome biogenesis. Like their Atg8 yeast ortholog, mammalian Atg8 proteins participate in cargo delivery into autophagosomes. Although the autophagic pathway in mammals has been referred to as a nonselective process, it seems that Atg8 proteins selectively target cytosolic components for lysosomal degradation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1716">18</a>]. Considerable progress in establishing this idea was achieved by the characterization of the ubiquitin-binding proteins p62/SQSTM1 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 94" title="Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T: p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005, 171: 603-614. 10.1083/jcb.200507002." href="/articles/10.1186/gb-2011-12-7-226#ref-CR94" id="ref-link-section-d86216623e1719">94</a>], neighbor of Brca1 (Nbr1) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 95" title="Kirkin V, Lamark T, Sou YS, Bjørkøy G, Nunn JL, Bruun JA, Shvets E, McEwan DG, Clausen TH, Wild P, Bilusic I, Theurillat JP, Øvervatn A, Ishii T, Elazar Z, Komatsu M, Dikic I, Johansen T: A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009, 33: 505-516. 10.1016/j.molcel.2009.01.020." href="/articles/10.1186/gb-2011-12-7-226#ref-CR95" id="ref-link-section-d86216623e1722">95</a>], the Bcl2-related protein Nix [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 96" title="Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Löhr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dötsch V, Ney PA, Dikic I: Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010, 11: 45-51. 10.1038/embor.2009.256." href="/articles/10.1186/gb-2011-12-7-226#ref-CR96" id="ref-link-section-d86216623e1725">96</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 97" title="Schwarten M, Mohrluder J, Ma P, Stoldt M, Thielmann Y, Stangler T, Hersch N, Hoffmann B, Merkel R, Willbold D: Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy. 2009, 5: 690-698. 10.4161/auto.5.5.8494." href="/articles/10.1186/gb-2011-12-7-226#ref-CR97" id="ref-link-section-d86216623e1728">97</a>], autophagy-linked FYVE protein (Alfy) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 98" title="Filimonenko M, Stuffers S, Raiborg C, Yamamoto A, Malerod L, Fisher EM, Isaacs A, Brech A, Stenmark H, Simonsen A: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol. 2007, 179: 485-500. 10.1083/jcb.200702115." href="/articles/10.1186/gb-2011-12-7-226#ref-CR98" id="ref-link-section-d86216623e1732">98</a>–<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 100" title="Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, Melia TJ, Bartlett BJ, Myers KM, Birkeland HC, Lamark T, Krainc D, Brech A, Stenmark H, Simonsen A, Yamamoto A: The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010, 38: 265-279. 10.1016/j.molcel.2010.04.007." href="/articles/10.1186/gb-2011-12-7-226#ref-CR100" id="ref-link-section-d86216623e1735">100</a>], nuclear dot protein 52 kDa (NDP52) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 101" title="Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F: The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol. 2009, 10: 1215-1221. 10.1038/ni.1800." href="/articles/10.1186/gb-2011-12-7-226#ref-CR101" id="ref-link-section-d86216623e1738">101</a>], and Optineurin [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 102" title="Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, Dötsch V, Bumann D, Dikic I: Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011, 333: 228-233. 10.1126/science.1205405." href="/articles/10.1186/gb-2011-12-7-226#ref-CR102" id="ref-link-section-d86216623e1741">102</a>] as autophagic receptors. These adaptors bind simultaneously to Atg8 proteins and to ubiquitinated proteins, organelles, and in some cases pathogens [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1744">18</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 94" title="Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T: p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005, 171: 603-614. 10.1083/jcb.200507002." href="/articles/10.1186/gb-2011-12-7-226#ref-CR94" id="ref-link-section-d86216623e1747">94</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 103" title="Shvets E, Fass E, Scherz-Shouval R, Elazar Z: The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes. J Cell Sci. 2008, 121: 2685-2695. 10.1242/jcs.026005." href="/articles/10.1186/gb-2011-12-7-226#ref-CR103" id="ref-link-section-d86216623e1751">103</a>]. The motif in p62 responsible for binding Atg8, the LC3-interacting region (LIR, also known as Atg8-interacting motif, AIM) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 104" title="Ichimura Y, Kumanomidou T, Sou YS, Mizushima T, Ezaki J, Ueno T, Kominami E, Yamane T, Tanaka K, Komatsu M: Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem. 2008, 283: 22847-22857. 10.1074/jbc.M802182200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR104" id="ref-link-section-d86216623e1754">104</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 105" title="Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007, 282: 24131-24145. 10.1074/jbc.M702824200." href="/articles/10.1186/gb-2011-12-7-226#ref-CR105" id="ref-link-section-d86216623e1757">105</a>], is common to other proteins that interact with Atg8 proteins, including Nbr1 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 106" title="Kraft C, Peter M, Hofmann K: Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol. 2010, 12: 836-841. 10.1038/ncb0910-836." href="/articles/10.1186/gb-2011-12-7-226#ref-CR106" id="ref-link-section-d86216623e1760">106</a>], Atg3 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 107" title="Yamaguchi M, Noda NN, Nakatogawa H, Kumeta H, Ohsumi Y, Inagaki F: Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3-Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway. J Biol Chem. 2010, 285: 29599-29607. 10.1074/jbc.M110.113670." href="/articles/10.1186/gb-2011-12-7-226#ref-CR107" id="ref-link-section-d86216623e1763">107</a>], Nix [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 96" title="Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Löhr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dötsch V, Ney PA, Dikic I: Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010, 11: 45-51. 10.1038/embor.2009.256." href="/articles/10.1186/gb-2011-12-7-226#ref-CR96" id="ref-link-section-d86216623e1766">96</a>] and the yeast cytoplasm-to-vacuole targeting receptor Atg19 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 108" title="Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, Fujioka Y, Ohsumi Y, Inagaki F: Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008, 13: 1211-1218. 10.1111/j.1365-2443.2008.01238.x." href="/articles/10.1186/gb-2011-12-7-226#ref-CR108" id="ref-link-section-d86216623e1770">108</a>].</p><p>Functional divergence of the Atg8 subfamilies is also inferred from specific interactions. Apparently, p62 binds both GATE-16 and LC3 in their soluble forms, but its interaction with LC3 but not with GATE-16 remains intact following their lipidation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 21" title="Shvets E, Abada A, Weidberg H, Elazar Z: Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes. Autophagy. 2011, 7: 683-688. 10.4161/auto.7.7.15279." href="/articles/10.1186/gb-2011-12-7-226#ref-CR21" id="ref-link-section-d86216623e1776">21</a>]. Thus, recruitment of p62 into autophagosomes specifically depends on LC3. This interaction, like other functions of Atg8 proteins, is dependent on the most variable region of these proteins, the amino terminus. Specificity of cargo recognition also applies to the GABARAP subfamily, as GABARAP-L1 binds to starch-binding-domain-containing protein 1, a carrier of glycogen. This interaction results in the arrival of glycogen at the lysosome and is therefore suggested to regulate cellular glucose levels [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 109" title="Jiang S, Heller B, Tagliabracci VS, Zhai L, Irimia JM, DePaoli-Roach AA, Wells CD, Skurat AV, Roach PJ: Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J Biol Chem. 2010, 285: 34960-34971. 10.1074/jbc.M110.150839." href="/articles/10.1186/gb-2011-12-7-226#ref-CR109" id="ref-link-section-d86216623e1779">109</a>]. The role of Atg8s during the autophagic process is depicted in Figure <a data-track="click" data-track-label="link" data-track-action="figure anchor" href="/articles/10.1186/gb-2011-12-7-226#Fig4">4b</a>.</p></div></div></section><section data-title="Frontiers"><div class="c-article-section" id="Sec8-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec8">Frontiers</h2><div class="c-article-section__content" id="Sec8-content"><p>Atg8 proteins act in diverse intracellular trafficking and autophagy processes. Although the number of Atg8 genes increases if one compares organisms that diverged early with those that diverged late in evolution, their conjugation to PE on the autophagic membrane remains a common feature conserved through evolution. Considerable scientific advancement over the past few years has revealed many Atg8 functions during autophagy, but has also raised many new questions. One major question is how these factors orchestrate their dual role in membrane fusion and cargo recruitment into autophagosomes.</p><p>Although mammalian cells are thought to have as many as eight Atg8 proteins, the exact number is not clear, largely because these factors do not show a unique pattern of expression. Although the mammalian Atg8 subfamilies seem to act differently during the formation of autophagosomes, the need for up to four members from each subfamily has yet to be revealed. In particular, it is crucial to determine whether different members of one subfamily occupy the same autophagosomes or whether each member acts in a distinct autophagosome. This may help in deciphering whether autophagy, induced by different stress conditions, results in the formation of 'specialized' autophagosomes containing distinct Atg8 members. Moreover, substantial proteomic data are needed to establish the cargo specificity of each Atg8 member. Selectivity of autophagy was recently reported for many organelles, such as peroxisomes (pexophagy), mitochondria (mitophagy) and ribosomes (ribophagy) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 18" title="Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552." href="/articles/10.1186/gb-2011-12-7-226#ref-CR18" id="ref-link-section-d86216623e1796">18</a>]. It is feasible that different members of the Atg8 family are crucial for selective autophagy. The role of Atg8s in intracellular trafficking has not been extensively studied. Some lines of evidence show that the conjugation of Atg8s, specifically GABARAPs, to PE is essential for their activity. This should be further investigated by testing the requirement of the Atg8 conjugation system for Golgi-to-plasma-membrane trafficking.</p><p>One major obstacle in studying the role of individual Atg8 family members is their high sequence similarity. This feature reduces the specificity of antibodies, as antibodies against GABARAP, for example, may interact with GABARAP-L1. It is therefore crucial to exploit unique epitopes within these proteins to construct novel specific antibodies. Furthermore, the overexpression approach is not optimal as LC3 proteins tend to form aggregates when transiently expressed [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 110" title="Kuma A, Matsui M, Mizushima N: LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization. Autophagy. 2007, 3: 323-328." href="/articles/10.1186/gb-2011-12-7-226#ref-CR110" id="ref-link-section-d86216623e1802">110</a>]. To overcome this pitfall, species that contain one Atg8 representative from each subfamily could be used to elucidate their role. Moreover, knockout mice of specific Atg8 subfamily members will help in dissecting these proteins' roles during development and in a tissue-specific manner. These are some of the questions and challenges that will be the focus of future studies.</p></div></div></section> <div id="MagazineFulltextArticleBodySuffix"><section aria-labelledby="Bib1" data-title="References"><div class="c-article-section" id="Bib1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Bib1">References</h2><div class="c-article-section__content" id="Bib1-content"><div data-container-section="references"><ol class="c-article-references" data-track-component="outbound reference" data-track-context="references section"><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="1."><p class="c-article-references__text" id="ref-CR1">Wood V, Gwilliam R, Rajandream MA, Lyne M, Lyne R, Stewart A, Sgouros J, Peat N, Hayles J, Baker S, Basham D, Bowman S, Brooks K, Brown D, Brown S, Chillingworth T, Churcher C, Collins M, Connor R, Cronin A, Davis P, Feltwell T, Fraser A, Gentles S, Goble A, Hamlin N, Harris D, Hidalgo J, Hodgson G, Holroyd S, et al: The genome sequence of <i>Schizosaccharomyces pombe</i>. Nature. 2002, 415: 871-880. 10.1038/nature724.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11859360" aria-label="PubMed reference 1">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD38Xhs1ygtbk%3D" aria-label="CAS reference 1">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 1" href="http://scholar.google.com/scholar_lookup?&title=The%20genome%20sequence%20of%20Schizosaccharomyces%20pombe&journal=Nature&doi=10.1038%2Fnature724&volume=415&pages=871-880&publication_year=2002&author=Wood%2CV&author=Gwilliam%2CR&author=Rajandream%2CMA&author=Lyne%2CM&author=Lyne%2CR&author=Stewart%2CA&author=Sgouros%2CJ&author=Peat%2CN&author=Hayles%2CJ&author=Baker%2CS&author=Basham%2CD&author=Bowman%2CS&author=Brooks%2CK&author=Brown%2CD&author=Brown%2CS&author=Chillingworth%2CT&author=Churcher%2CC&author=Collins%2CM&author=Connor%2CR&author=Cronin%2CA&author=Davis%2CP&author=Feltwell%2CT&author=Fraser%2CA&author=Gentles%2CS&author=Goble%2CA&author=Hamlin%2CN&author=Harris%2CD&author=Hidalgo%2CJ&author=Hodgson%2CG&author=Holroyd%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="2."><p class="c-article-references__text" id="ref-CR2">VectorBase: <i>I. scapularis</i>. [<a href="http://iscapularis.vectorbase.org/" data-track="click_references" data-track-action="external reference" data-track-value="external reference" data-track-label="http://iscapularis.vectorbase.org/">http://iscapularis.vectorbase.org/</a>]</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="3."><p class="c-article-references__text" id="ref-CR3">Insights into social insects from the genome of the honeybee <i>Apis mellifera</i>. Nature. 2006, 443: 931-949. 10.1038/nature05260.</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="4."><p class="c-article-references__text" id="ref-CR4">A Database of <i>Drosophila</i> Genes & Genomes. [<a href="http://flybase.org/" data-track="click_references" data-track-action="external reference" data-track-value="external reference" data-track-label="http://flybase.org/">http://flybase.org/</a>]</p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="5."><p class="c-article-references__text" id="ref-CR5">Srivastava M, Simakov O, Chapman J, Fahey B, Gauthier ME, Mitros T, Richards GS, Conaco C, Dacre M, Hellsten U, Larroux C, Putnam NH, Stanke M, Adamska M, Darling A, Degnan SM, Oakley TH, Plachetzki DC, Zhai Y, Adamski M, Calcino A, Cummins SF, Goodstein DM, Harris C, Jackson DJ, Leys SP, Shu S, Woodcroft BJ, Vervoort M, Kosik KS, et al: The <i>Amphimedon queenslandica</i> genome and the evolution of animal complexity. Nature. 2010, 466: 720-726. 10.1038/nature09201.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20686567" aria-label="PubMed reference 5">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtVSmurfP" aria-label="CAS reference 5">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130542" aria-label="PubMed Central reference 5">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 5" href="http://scholar.google.com/scholar_lookup?&title=The%20Amphimedon%20queenslandica%20genome%20and%20the%20evolution%20of%20animal%20complexity&journal=Nature&doi=10.1038%2Fnature09201&volume=466&pages=720-726&publication_year=2010&author=Srivastava%2CM&author=Simakov%2CO&author=Chapman%2CJ&author=Fahey%2CB&author=Gauthier%2CME&author=Mitros%2CT&author=Richards%2CGS&author=Conaco%2CC&author=Dacre%2CM&author=Hellsten%2CU&author=Larroux%2CC&author=Putnam%2CNH&author=Stanke%2CM&author=Adamska%2CM&author=Darling%2CA&author=Degnan%2CSM&author=Oakley%2CTH&author=Plachetzki%2CDC&author=Zhai%2CY&author=Adamski%2CM&author=Calcino%2CA&author=Cummins%2CSF&author=Goodstein%2CDM&author=Harris%2CC&author=Jackson%2CDJ&author=Leys%2CSP&author=Shu%2CS&author=Woodcroft%2CBJ&author=Vervoort%2CM&author=Kosik%2CKS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="6."><p class="c-article-references__text" id="ref-CR6">King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nichols S, Richter DJ, Salamov A, Sequencing JG, Bork P, Lim WA, Manning G, et al: The genome of the choanoflagellate <i>Monosiga brevicollis</i> and the origin of metazoans. Nature. 2008, 451: 783-788. 10.1038/nature06617.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18273011" aria-label="PubMed reference 6">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXhvVylur0%3D" aria-label="CAS reference 6">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562698" aria-label="PubMed Central reference 6">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 6" href="http://scholar.google.com/scholar_lookup?&title=The%20genome%20of%20the%20choanoflagellate%20Monosiga%20brevicollis%20and%20the%20origin%20of%20metazoans&journal=Nature&doi=10.1038%2Fnature06617&volume=451&pages=783-788&publication_year=2008&author=King%2CN&author=Westbrook%2CMJ&author=Young%2CSL&author=Kuo%2CA&author=Abedin%2CM&author=Chapman%2CJ&author=Fairclough%2CS&author=Hellsten%2CU&author=Isogai%2CY&author=Letunic%2CI&author=Marr%2CM&author=Pincus%2CD&author=Putnam%2CN&author=Rokas%2CA&author=Wright%2CKJ&author=Zuzow%2CR&author=Dirks%2CW&author=Good%2CM&author=Goodstein%2CD&author=Lemons%2CD&author=Li%2CW&author=Lyons%2CJB&author=Morris%2CA&author=Nichols%2CS&author=Richter%2CDJ&author=Salamov%2CA&author=Sequencing%2CJG&author=Bork%2CP&author=Lim%2CWA&author=Manning%2CG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="7."><p class="c-article-references__text" id="ref-CR7">Sláviková S, Shy G, Yao Y, Glozman R, Levanony H, Pietrokovski S, Elazar Z, Galili G: The autophagy-associated Atg8 gene family operates both under favorable growth conditions and under starvation stresses in <i>Arabidopsis</i> plants. J Exp Bot. 2005, 56: 2839-2849. 10.1093/jxb/eri276.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16157655" aria-label="PubMed reference 7">PubMed</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 7" href="http://scholar.google.com/scholar_lookup?&title=The%20autophagy-associated%20Atg8%20gene%20family%20operates%20both%20under%20favorable%20growth%20conditions%20and%20under%20starvation%20stresses%20in%20Arabidopsis%20plants&journal=J%20Exp%20Bot&doi=10.1093%2Fjxb%2Feri276&volume=56&pages=2839-2849&publication_year=2005&author=Sl%C3%A1vikov%C3%A1%2CS&author=Shy%2CG&author=Yao%2CY&author=Glozman%2CR&author=Levanony%2CH&author=Pietrokovski%2CS&author=Elazar%2CZ&author=Galili%2CG"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="8."><p class="c-article-references__text" id="ref-CR8">Coyle JE, Qamar S, Rajashankar KR, Nikolov DB: Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding. Neuron. 2002, 33: 63-74. 10.1016/S0896-6273(01)00558-X.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11779480" aria-label="PubMed reference 8">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD38XksFSitg%3D%3D" aria-label="CAS reference 8">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 8" href="http://scholar.google.com/scholar_lookup?&title=Structure%20of%20GABARAP%20in%20two%20conformations%3A%20implications%20for%20GABA%28A%29%20receptor%20localization%20and%20tubulin%20binding&journal=Neuron&doi=10.1016%2FS0896-6273%2801%2900558-X&volume=33&pages=63-74&publication_year=2002&author=Coyle%2CJE&author=Qamar%2CS&author=Rajashankar%2CKR&author=Nikolov%2CDB"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="9."><p class="c-article-references__text" id="ref-CR9">Hu C, Zhang X, Teng YB, Hu HX, Li WF: Structure of autophagy-related protein Atg8 from the silkworm <i>Bombyx mori</i>. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010, 66: 787-790. 10.1107/S1744309110018464.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20606273" aria-label="PubMed reference 9">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXosVKju7Y%3D" aria-label="CAS reference 9">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898461" aria-label="PubMed Central reference 9">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 9" href="http://scholar.google.com/scholar_lookup?&title=Structure%20of%20autophagy-related%20protein%20Atg8%20from%20the%20silkworm%20Bombyx%20mori&journal=Acta%20Crystallogr%20Sect%20F%20Struct%20Biol%20Cryst%20Commun&doi=10.1107%2FS1744309110018464&volume=66&pages=787-790&publication_year=2010&author=Hu%2CC&author=Zhang%2CX&author=Teng%2CYB&author=Hu%2CHX&author=Li%2CWF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="10."><p class="c-article-references__text" id="ref-CR10">Koopmann R, Muhammad K, Perbandt M, Betzel C, Duszenko M: <i>Trypanosoma brucei</i> ATG8: structural insights into autophagic-like mechanisms in protozoa. Autophagy. 2009, 5: 1085-1091. 10.4161/auto.5.8.9611.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19736525" aria-label="PubMed reference 10">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXkvVeitro%3D" aria-label="CAS reference 10">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 10" href="http://scholar.google.com/scholar_lookup?&title=Trypanosoma%20brucei%20ATG8%3A%20structural%20insights%20into%20autophagic-like%20mechanisms%20in%20protozoa&journal=Autophagy&doi=10.4161%2Fauto.5.8.9611&volume=5&pages=1085-1091&publication_year=2009&author=Koopmann%2CR&author=Muhammad%2CK&author=Perbandt%2CM&author=Betzel%2CC&author=Duszenko%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="11."><p class="c-article-references__text" id="ref-CR11">Kouno T, Mizuguchi M, Tanida I, Ueno T, Kanematsu T, Mori Y, Shinoda H, Hirata M, Kominami E, Kawano K: Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains. J Biol Chem. 2005, 280: 24610-24617. 10.1074/jbc.M413565200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15857831" aria-label="PubMed reference 11">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXlsFyru7k%3D" aria-label="CAS reference 11">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 11" href="http://scholar.google.com/scholar_lookup?&title=Solution%20structure%20of%20microtubule-associated%20protein%20light%20chain%203%20and%20identification%20of%20its%20functional%20subdomains&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M413565200&volume=280&pages=24610-24617&publication_year=2005&author=Kouno%2CT&author=Mizuguchi%2CM&author=Tanida%2CI&author=Ueno%2CT&author=Kanematsu%2CT&author=Mori%2CY&author=Shinoda%2CH&author=Hirata%2CM&author=Kominami%2CE&author=Kawano%2CK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="12."><p class="c-article-references__text" id="ref-CR12">Kumeta H, Watanabe M, Nakatogawa H, Yamaguchi M, Ogura K, Adachi W, Fujioka Y, Noda NN, Ohsumi Y, Inagaki F: The NMR structure of the autophagy-related protein Atg8. J Biomol NMR. 2010, 47: 237-241. 10.1007/s10858-010-9420-1.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20428927" aria-label="PubMed reference 12">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXns1WqtbY%3D" aria-label="CAS reference 12">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 12" href="http://scholar.google.com/scholar_lookup?&title=The%20NMR%20structure%20of%20the%20autophagy-related%20protein%20Atg8&journal=J%20Biomol%20NMR&doi=10.1007%2Fs10858-010-9420-1&volume=47&pages=237-241&publication_year=2010&author=Kumeta%2CH&author=Watanabe%2CM&author=Nakatogawa%2CH&author=Yamaguchi%2CM&author=Ogura%2CK&author=Adachi%2CW&author=Fujioka%2CY&author=Noda%2CNN&author=Ohsumi%2CY&author=Inagaki%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="13."><p class="c-article-references__text" id="ref-CR13">Paz Y, Elazar Z, Fass D: Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p. J Biol Chem. 2000, 275: 25445-25450. 10.1074/jbc.C000307200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10856287" aria-label="PubMed reference 13">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXmtVehs7c%3D" aria-label="CAS reference 13">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 13" href="http://scholar.google.com/scholar_lookup?&title=Structure%20of%20GATE-16%2C%20membrane%20transport%20modulator%20and%20mammalian%20ortholog%20of%20autophagocytosis%20factor%20Aut7p&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.C000307200&volume=275&pages=25445-25450&publication_year=2000&author=Paz%2CY&author=Elazar%2CZ&author=Fass%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="14."><p class="c-article-references__text" id="ref-CR14">Schwarten M, Stoldt M, Mohrluder J, Willbold D: Solution structure of Atg8 reveals conformational polymorphism of the N-terminal domain. Biochem Biophys Res Commun. 2010, 395: 426-431. 10.1016/j.bbrc.2010.04.043.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20382112" aria-label="PubMed reference 14">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXlvVGntL0%3D" aria-label="CAS reference 14">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 14" href="http://scholar.google.com/scholar_lookup?&title=Solution%20structure%20of%20Atg8%20reveals%20conformational%20polymorphism%20of%20the%20N-terminal%20domain&journal=Biochem%20Biophys%20Res%20Commun&doi=10.1016%2Fj.bbrc.2010.04.043&volume=395&pages=426-431&publication_year=2010&author=Schwarten%2CM&author=Stoldt%2CM&author=Mohrluder%2CJ&author=Willbold%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="15."><p class="c-article-references__text" id="ref-CR15">Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F: The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of <i>Saccharomyces cerevisiae</i> Atg8. Genes Cells. 2004, 9: 611-618. 10.1111/j.1356-9597.2004.00750.x.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15265004" aria-label="PubMed reference 15">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXmtlKntL0%3D" aria-label="CAS reference 15">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 15" href="http://scholar.google.com/scholar_lookup?&title=The%20crystal%20structure%20of%20microtubule-associated%20protein%20light%20chain%203%2C%20a%20mammalian%20homologue%20of%20Saccharomyces%20cerevisiae%20Atg8&journal=Genes%20Cells&doi=10.1111%2Fj.1356-9597.2004.00750.x&volume=9&pages=611-618&publication_year=2004&author=Sugawara%2CK&author=Suzuki%2CNN&author=Fujioka%2CY&author=Mizushima%2CN&author=Ohsumi%2CY&author=Inagaki%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="16."><p class="c-article-references__text" id="ref-CR16">Noda NN, Ohsumi Y, Inagaki F: ATG systems from the protein structural point of view. Chem Rev. 2009, 109: 1587-1598. 10.1021/cr800459r.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19236009" aria-label="PubMed reference 16">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXit1elsb0%3D" aria-label="CAS reference 16">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 16" href="http://scholar.google.com/scholar_lookup?&title=ATG%20systems%20from%20the%20protein%20structural%20point%20of%20view&journal=Chem%20Rev&doi=10.1021%2Fcr800459r&volume=109&pages=1587-1598&publication_year=2009&author=Noda%2CNN&author=Ohsumi%2CY&author=Inagaki%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="17."><p class="c-article-references__text" id="ref-CR17">Bavro VN, Sola M, Bracher A, Kneussel M, Betz H, Weissenhorn W: Crystal structure of the GABA(A)-receptor-associated protein, GABARAP. EMBO Rep. 2002, 3: 183-189. 10.1093/embo-reports/kvf026.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11818336" aria-label="PubMed reference 17">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD38XitVGqtrk%3D" aria-label="CAS reference 17">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083967" aria-label="PubMed Central reference 17">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 17" href="http://scholar.google.com/scholar_lookup?&title=Crystal%20structure%20of%20the%20GABA%28A%29-receptor-associated%20protein%2C%20GABARAP&journal=EMBO%20Rep&doi=10.1093%2Fembo-reports%2Fkvf026&volume=3&pages=183-189&publication_year=2002&author=Bavro%2CVN&author=Sola%2CM&author=Bracher%2CA&author=Kneussel%2CM&author=Betz%2CH&author=Weissenhorn%2CW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="18."><p class="c-article-references__text" id="ref-CR18">Weidberg H, Shvets E, Elazar Z: Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011, 80: 125-156. 10.1146/annurev-biochem-052709-094552.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21548784" aria-label="PubMed reference 18">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXptVCns70%3D" aria-label="CAS reference 18">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 18" href="http://scholar.google.com/scholar_lookup?&title=Biogenesis%20and%20cargo%20selectivity%20of%20autophagosomes&journal=Annu%20Rev%20Biochem&doi=10.1146%2Fannurev-biochem-052709-094552&volume=80&pages=125-156&publication_year=2011&author=Weidberg%2CH&author=Shvets%2CE&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="19."><p class="c-article-references__text" id="ref-CR19">Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y: <i>In vivo</i> and <i>in vitro</i> reconstitution of Atg8 conjugation essential for autophagy. J Biol Chem. 2004, 279: 40584-40592. 10.1074/jbc.M405860200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15277523" aria-label="PubMed reference 19">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXnslWntr8%3D" aria-label="CAS reference 19">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 19" href="http://scholar.google.com/scholar_lookup?&title=In%20vivo%20and%20in%20vitro%20reconstitution%20of%20Atg8%20conjugation%20essential%20for%20autophagy&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M405860200&volume=279&pages=40584-40592&publication_year=2004&author=Ichimura%2CY&author=Imamura%2CY&author=Emoto%2CK&author=Umeda%2CM&author=Noda%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="20."><p class="c-article-references__text" id="ref-CR20">Nakatogawa H, Ichimura Y, Ohsumi Y: Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell. 2007, 130: 165-178. 10.1016/j.cell.2007.05.021.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17632063" aria-label="PubMed reference 20">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXotlGmt7o%3D" aria-label="CAS reference 20">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 20" href="http://scholar.google.com/scholar_lookup?&title=Atg8%2C%20a%20ubiquitin-like%20protein%20required%20for%20autophagosome%20formation%2C%20mediates%20membrane%20tethering%20and%20hemifusion&journal=Cell&doi=10.1016%2Fj.cell.2007.05.021&volume=130&pages=165-178&publication_year=2007&author=Nakatogawa%2CH&author=Ichimura%2CY&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="21."><p class="c-article-references__text" id="ref-CR21">Shvets E, Abada A, Weidberg H, Elazar Z: Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes. Autophagy. 2011, 7: 683-688. 10.4161/auto.7.7.15279.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21460636" aria-label="PubMed reference 21">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC38XhtFCis7o%3D" aria-label="CAS reference 21">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 21" href="http://scholar.google.com/scholar_lookup?&title=Dissecting%20the%20involvement%20of%20LC3B%20and%20GATE-16%20in%20p62%20recruitment%20into%20autophagosomes&journal=Autophagy&doi=10.4161%2Fauto.7.7.15279&volume=7&pages=683-688&publication_year=2011&author=Shvets%2CE&author=Abada%2CA&author=Weidberg%2CH&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="22."><p class="c-article-references__text" id="ref-CR22">Weidberg H, Shpilka T, Shvets E, Abada A, Shimron F, Elazar Z: LC3 and GATE-16 N termini mediate membrane fusion processes required for autophagosome biogenesis. Dev Cell. 2011, 20: 444-454. 10.1016/j.devcel.2011.02.006.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21497758" aria-label="PubMed reference 22">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXkvVCru7s%3D" aria-label="CAS reference 22">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 22" href="http://scholar.google.com/scholar_lookup?&title=LC3%20and%20GATE-16%20N%20termini%20mediate%20membrane%20fusion%20processes%20required%20for%20autophagosome%20biogenesis&journal=Dev%20Cell&doi=10.1016%2Fj.devcel.2011.02.006&volume=20&pages=444-454&publication_year=2011&author=Weidberg%2CH&author=Shpilka%2CT&author=Shvets%2CE&author=Abada%2CA&author=Shimron%2CF&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="23."><p class="c-article-references__text" id="ref-CR23">He H, Dang Y, Dai F, Guo Z, Wu J, She X, Pei Y, Chen Y, Ling W, Wu C, Zhao S, Liu JO, Yu L: Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B. J Biol Chem. 2003, 278: 29278-29287. 10.1074/jbc.M303800200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12740394" aria-label="PubMed reference 23">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXlsl2mt70%3D" aria-label="CAS reference 23">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 23" href="http://scholar.google.com/scholar_lookup?&title=Post-translational%20modifications%20of%20three%20members%20of%20the%20human%20MAP1LC3%20family%20and%20detection%20of%20a%20novel%20type%20of%20modification%20for%20MAP1LC3B&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M303800200&volume=278&pages=29278-29287&publication_year=2003&author=He%2CH&author=Dang%2CY&author=Dai%2CF&author=Guo%2CZ&author=Wu%2CJ&author=She%2CX&author=Pei%2CY&author=Chen%2CY&author=Ling%2CW&author=Wu%2CC&author=Zhao%2CS&author=Liu%2CJO&author=Yu%2CL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="24."><p class="c-article-references__text" id="ref-CR24">Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S: Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein. Genomics. 2001, 74: 408-413. 10.1006/geno.2001.6555.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11414770" aria-label="PubMed reference 24">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3MXksVChs7Y%3D" aria-label="CAS reference 24">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 24" href="http://scholar.google.com/scholar_lookup?&title=Cloning%2C%20expression%20patterns%2C%20and%20chromosome%20localization%20of%20three%20human%20and%20two%20mouse%20homologues%20of%20GABA%28A%29%20receptor-associated%20protein&journal=Genomics&doi=10.1006%2Fgeno.2001.6555&volume=74&pages=408-413&publication_year=2001&author=Xin%2CY&author=Yu%2CL&author=Chen%2CZ&author=Zheng%2CL&author=Fu%2CQ&author=Jiang%2CJ&author=Zhang%2CP&author=Gong%2CR&author=Zhao%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="25."><p class="c-article-references__text" id="ref-CR25">Nemos C, Mansuy V, Vernier-Magnin S, Fraichard A, Jouvenot M, Delage-Mourroux R: Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system. Brain Res Mol Brain Res. 2003, 119: 216-219.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14625090" aria-label="PubMed reference 25">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXptVSit7c%3D" aria-label="CAS reference 25">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 25" href="http://scholar.google.com/scholar_lookup?&title=Expression%20of%20gec1%2FGABARAPL1%20versus%20GABARAP%20mRNAs%20in%20human%3A%20predominance%20of%20gec1%2FGABARAPL1%20in%20the%20central%20nervous%20system&journal=Brain%20Res%20Mol%20Brain%20Res&volume=119&pages=216-219&publication_year=2003&author=Nemos%2CC&author=Mansuy%2CV&author=Vernier-Magnin%2CS&author=Fraichard%2CA&author=Jouvenot%2CM&author=Delage-Mourroux%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="26."><p class="c-article-references__text" id="ref-CR26">Sagiv Y, Legesse-Miller A, Porat A, Elazar Z: GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J. 2000, 19: 1494-1504. 10.1093/emboj/19.7.1494.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10747018" aria-label="PubMed reference 26">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXislymtrk%3D" aria-label="CAS reference 26">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC310219" aria-label="PubMed Central reference 26">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 26" href="http://scholar.google.com/scholar_lookup?&title=GATE-16%2C%20a%20membrane%20transport%20modulator%2C%20interacts%20with%20NSF%20and%20the%20Golgi%20v-SNARE%20GOS-28&journal=EMBO%20J&doi=10.1093%2Femboj%2F19.7.1494&volume=19&pages=1494-1504&publication_year=2000&author=Sagiv%2CY&author=Legesse-Miller%2CA&author=Porat%2CA&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="27."><p class="c-article-references__text" id="ref-CR27">Egami Y, Kiryu-Seo S, Yoshimori T, Kiyama H: Induced expressions of Rab24 GTPase and LC3 in nerve-injured motor neurons. Biochem Biophys Res Commun. 2005, 337: 1206-1213. 10.1016/j.bbrc.2005.09.171.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16236257" aria-label="PubMed reference 27">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXhtFKhs7fM" aria-label="CAS reference 27">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 27" href="http://scholar.google.com/scholar_lookup?&title=Induced%20expressions%20of%20Rab24%20GTPase%20and%20LC3%20in%20nerve-injured%20motor%20neurons&journal=Biochem%20Biophys%20Res%20Commun&doi=10.1016%2Fj.bbrc.2005.09.171&volume=337&pages=1206-1213&publication_year=2005&author=Egami%2CY&author=Kiryu-Seo%2CS&author=Yoshimori%2CT&author=Kiyama%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="28."><p class="c-article-references__text" id="ref-CR28">Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, Noda T, Ohsumi Y: Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999, 147: 435-446. 10.1083/jcb.147.2.435.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10525546" aria-label="PubMed reference 28">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1MXmslCqsLw%3D" aria-label="CAS reference 28">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174223" aria-label="PubMed Central reference 28">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 28" href="http://scholar.google.com/scholar_lookup?&title=Formation%20process%20of%20autophagosome%20is%20traced%20with%20Apg8%2FAut7p%20in%20yeast&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.147.2.435&volume=147&pages=435-446&publication_year=1999&author=Kirisako%2CT&author=Baba%2CM&author=Ishihara%2CN&author=Miyazawa%2CK&author=Ohsumi%2CM&author=Yoshimori%2CT&author=Noda%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="29."><p class="c-article-references__text" id="ref-CR29">Zois CE, Giatromanolaki A, Kainulainen H, Botaitis S, Torvinen S, Simopoulos C, Kortsaris A, Sivridis E, Koukourakis MI: Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine. Biochem Biophys Res Commun. 2011, 404: 552-558. 10.1016/j.bbrc.2010.12.024.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21145309" aria-label="PubMed reference 29">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXksF2gsw%3D%3D" aria-label="CAS reference 29">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 29" href="http://scholar.google.com/scholar_lookup?&title=Lung%20autophagic%20response%20following%20exposure%20of%20mice%20to%20whole%20body%20irradiation%2C%20with%20and%20without%20amifostine&journal=Biochem%20Biophys%20Res%20Commun&doi=10.1016%2Fj.bbrc.2010.12.024&volume=404&pages=552-558&publication_year=2011&author=Zois%2CCE&author=Giatromanolaki%2CA&author=Kainulainen%2CH&author=Botaitis%2CS&author=Torvinen%2CS&author=Simopoulos%2CC&author=Kortsaris%2CA&author=Sivridis%2CE&author=Koukourakis%2CMI"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="30."><p class="c-article-references__text" id="ref-CR30">van Zutphen T, Baerends RJ, Susanna KA, de Jong A, Kuipers OP, Veenhuis M, van der Klei IJ: Adaptation of <i>Hansenula polymorpha</i> to methanol: a transcriptome analysis. BMC Genomics. 2010, 11: 1-10.1186/1471-2164-11-1.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20044946" aria-label="PubMed reference 30">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827406" aria-label="PubMed Central reference 30">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 30" href="http://scholar.google.com/scholar_lookup?&title=Adaptation%20of%20Hansenula%20polymorpha%20to%20methanol%3A%20a%20transcriptome%20analysis&journal=BMC%20Genomics&doi=10.1186%2F1471-2164-11-1&volume=11&publication_year=2010&author=van%20Zutphen%2CT&author=Baerends%2CRJ&author=Susanna%2CKA&author=de%20Jong%2CA&author=Kuipers%2COP&author=Veenhuis%2CM&author=van%20der%20Klei%2CIJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="31."><p class="c-article-references__text" id="ref-CR31">Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M: FoxO3 controls autophagy in skeletal muscle <i>in vivo</i>. Cell Metab. 2007, 6: 458-471. 10.1016/j.cmet.2007.11.001.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18054315" aria-label="PubMed reference 31">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhsVektb%2FN" aria-label="CAS reference 31">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 31" href="http://scholar.google.com/scholar_lookup?&title=FoxO3%20controls%20autophagy%20in%20skeletal%20muscle%20in%20vivo&journal=Cell%20Metab&doi=10.1016%2Fj.cmet.2007.11.001&volume=6&pages=458-471&publication_year=2007&author=Mammucari%2CC&author=Milan%2CG&author=Romanello%2CV&author=Masiero%2CE&author=Rudolf%2CR&author=Del%20Piccolo%2CP&author=Burden%2CSJ&author=Di%20Lisi%2CR&author=Sandri%2CC&author=Zhao%2CJ&author=Goldberg%2CAL&author=Schiaffino%2CS&author=Sandri%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="32."><p class="c-article-references__text" id="ref-CR32">Polager S, Ofir M, Ginsberg D: E2F1 regulates autophagy and the transcription of autophagy genes. Oncogene. 2008, 27: 4860-4864. 10.1038/onc.2008.117.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18408756" aria-label="PubMed reference 32">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXpvVSqtbo%3D" aria-label="CAS reference 32">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 32" href="http://scholar.google.com/scholar_lookup?&title=E2F1%20regulates%20autophagy%20and%20the%20transcription%20of%20autophagy%20genes&journal=Oncogene&doi=10.1038%2Fonc.2008.117&volume=27&pages=4860-4864&publication_year=2008&author=Polager%2CS&author=Ofir%2CM&author=Ginsberg%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="33."><p class="c-article-references__text" id="ref-CR33">Sengupta A, Molkentin JD, Yutzey KE: FoxO transcription factors promote autophagy in cardiomyocytes. J Biol Chem. 2009, 284: 28319-28331. 10.1074/jbc.M109.024406.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19696026" aria-label="PubMed reference 33">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXht1SqsbvP" aria-label="CAS reference 33">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788882" aria-label="PubMed Central reference 33">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 33" href="http://scholar.google.com/scholar_lookup?&title=FoxO%20transcription%20factors%20promote%20autophagy%20in%20cardiomyocytes&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M109.024406&volume=284&pages=28319-28331&publication_year=2009&author=Sengupta%2CA&author=Molkentin%2CJD&author=Yutzey%2CKE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="34."><p class="c-article-references__text" id="ref-CR34">Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, Lecker SH, Goldberg AL: FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007, 6: 472-483. 10.1016/j.cmet.2007.11.004.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18054316" aria-label="PubMed reference 34">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhsVektb%2FI" aria-label="CAS reference 34">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 34" href="http://scholar.google.com/scholar_lookup?&title=FoxO3%20coordinately%20activates%20protein%20degradation%20by%20the%20autophagic%2Flysosomal%20and%20proteasomal%20pathways%20in%20atrophying%20muscle%20cells&journal=Cell%20Metab&doi=10.1016%2Fj.cmet.2007.11.004&volume=6&pages=472-483&publication_year=2007&author=Zhao%2CJ&author=Brault%2CJJ&author=Schild%2CA&author=Cao%2CP&author=Sandri%2CM&author=Schiaffino%2CS&author=Lecker%2CSH&author=Goldberg%2CAL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="35."><p class="c-article-references__text" id="ref-CR35">Elazar Z, Scherz-Shouval R, Shorer H: Involvement of LMA1 and GATE-16 family members in intracellular membrane dynamics. Biochim Biophys Acta. 2003, 1641: 145-156. 10.1016/S0167-4889(03)00086-7.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12914955" aria-label="PubMed reference 35">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXmt1Gru78%3D" aria-label="CAS reference 35">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 35" href="http://scholar.google.com/scholar_lookup?&title=Involvement%20of%20LMA1%20and%20GATE-16%20family%20members%20in%20intracellular%20membrane%20dynamics&journal=Biochim%20Biophys%20Acta&doi=10.1016%2FS0167-4889%2803%2900086-7&volume=1641&pages=145-156&publication_year=2003&author=Elazar%2CZ&author=Scherz-Shouval%2CR&author=Shorer%2CH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="36."><p class="c-article-references__text" id="ref-CR36">Legesse-Miller A, Sagiv Y, Porat A, Elazar Z: Isolation and characterization of a novel low molecular weight protein involved in intra-Golgi traffic. J Biol Chem. 1998, 273: 3105-3109. 10.1074/jbc.273.5.3105.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9446628" aria-label="PubMed reference 36">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1cXnvFWjsA%3D%3D" aria-label="CAS reference 36">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 36" href="http://scholar.google.com/scholar_lookup?&title=Isolation%20and%20characterization%20of%20a%20novel%20low%20molecular%20weight%20protein%20involved%20in%20intra-Golgi%20traffic&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.273.5.3105&volume=273&pages=3105-3109&publication_year=1998&author=Legesse-Miller%2CA&author=Sagiv%2CY&author=Porat%2CA&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="37."><p class="c-article-references__text" id="ref-CR37">Muller JM, Shorter J, Newman R, Deinhardt K, Sagiv Y, Elazar Z, Warren G, Shima DT: Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion. J Cell Biol. 2002, 157: 1161-1173. 10.1083/jcb.200202082.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12070132" aria-label="PubMed reference 37">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173554" aria-label="PubMed Central reference 37">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 37" href="http://scholar.google.com/scholar_lookup?&title=Sequential%20SNARE%20disassembly%20and%20GATE-16-GOS-28%20complex%20assembly%20mediated%20by%20distinct%20NSF%20activities%20drives%20Golgi%20membrane%20fusion&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.200202082&volume=157&pages=1161-1173&publication_year=2002&author=Muller%2CJM&author=Shorter%2CJ&author=Newman%2CR&author=Deinhardt%2CK&author=Sagiv%2CY&author=Elazar%2CZ&author=Warren%2CG&author=Shima%2CDT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="38."><p class="c-article-references__text" id="ref-CR38">Kuznetsov SA, Gelfand VI: 18 kDa microtubule-associated protein: identification as a new light chain (LC-3) of microtubule-associated protein 1 (MAP-1). FEBS Lett. 1987, 212: 145-148. 10.1016/0014-5793(87)81574-0.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=3803603" aria-label="PubMed reference 38">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaL2sXhtFGnt7c%3D" aria-label="CAS reference 38">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 38" href="http://scholar.google.com/scholar_lookup?&title=18%20kDa%20microtubule-associated%20protein%3A%20identification%20as%20a%20new%20light%20chain%20%28LC-3%29%20of%20microtubule-associated%20protein%201%20%28MAP-1%29&journal=FEBS%20Lett&doi=10.1016%2F0014-5793%2887%2981574-0&volume=212&pages=145-148&publication_year=1987&author=Kuznetsov%2CSA&author=Gelfand%2CVI"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="39."><p class="c-article-references__text" id="ref-CR39">Mann SS, Hammarback JA: Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B. J Biol Chem. 1994, 269: 11492-11497.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7908909" aria-label="PubMed reference 39">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK2cXkt1yhsLo%3D" aria-label="CAS reference 39">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 39" href="http://scholar.google.com/scholar_lookup?&title=Molecular%20characterization%20of%20light%20chain%203.%20A%20microtubule%20binding%20subunit%20of%20MAP1A%20and%20MAP1B&journal=J%20Biol%20Chem&volume=269&pages=11492-11497&publication_year=1994&author=Mann%2CSS&author=Hammarback%2CJA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="40."><p class="c-article-references__text" id="ref-CR40">Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW: GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature. 1999, 397: 69-72. 10.1038/16264.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9892355" aria-label="PubMed reference 40">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1MXns1WrsQ%3D%3D" aria-label="CAS reference 40">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 40" href="http://scholar.google.com/scholar_lookup?&title=GABA%28A%29-receptor-associated%20protein%20links%20GABA%28A%29%20receptors%20and%20the%20cytoskeleton&journal=Nature&doi=10.1038%2F16264&volume=397&pages=69-72&publication_year=1999&author=Wang%2CH&author=Bedford%2CFK&author=Brandon%2CNJ&author=Moss%2CSJ&author=Olsen%2CRW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="41."><p class="c-article-references__text" id="ref-CR41">Leil TA, Chen ZW, Chang CS, Olsen RW: GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons. J Neurosci. 2004, 24: 11429-11438. 10.1523/JNEUROSCI.3355-04.2004.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15601949" aria-label="PubMed reference 41">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2MXjtVajsQ%3D%3D" aria-label="CAS reference 41">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 41" href="http://scholar.google.com/scholar_lookup?&title=GABAA%20receptor-associated%20protein%20traffics%20GABAA%20receptors%20to%20the%20plasma%20membrane%20in%20neurons&journal=J%20Neurosci&doi=10.1523%2FJNEUROSCI.3355-04.2004&volume=24&pages=11429-11438&publication_year=2004&author=Leil%2CTA&author=Chen%2CZW&author=Chang%2CCS&author=Olsen%2CRW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="42."><p class="c-article-references__text" id="ref-CR42">Chen ZW, Chang CS, Leil TA, Olsen RW: C-terminal modification is required for GABARAP-mediated GABA(A) receptor trafficking. J Neurosci. 2007, 27: 6655-6663. 10.1523/JNEUROSCI.0919-07.2007.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17581952" aria-label="PubMed reference 42">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXnsVWqsrk%3D" aria-label="CAS reference 42">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 42" href="http://scholar.google.com/scholar_lookup?&title=C-terminal%20modification%20is%20required%20for%20GABARAP-mediated%20GABA%28A%29%20receptor%20trafficking&journal=J%20Neurosci&doi=10.1523%2FJNEUROSCI.0919-07.2007&volume=27&pages=6655-6663&publication_year=2007&author=Chen%2CZW&author=Chang%2CCS&author=Leil%2CTA&author=Olsen%2CRW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="43."><p class="c-article-references__text" id="ref-CR43">Green F, O'Hare T, Blackwell A, Enns CA: Association of human transferrin receptor with GABARAP. FEBS Lett. 2002, 518: 101-106. 10.1016/S0014-5793(02)02655-8.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11997026" aria-label="PubMed reference 43">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD38XjsVSrs7w%3D" aria-label="CAS reference 43">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 43" href="http://scholar.google.com/scholar_lookup?&title=Association%20of%20human%20transferrin%20receptor%20with%20GABARAP&journal=FEBS%20Lett&doi=10.1016%2FS0014-5793%2802%2902655-8&volume=518&pages=101-106&publication_year=2002&author=Green%2CF&author=O%27Hare%2CT&author=Blackwell%2CA&author=Enns%2CCA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="44."><p class="c-article-references__text" id="ref-CR44">Nakamura T, Hayashi T, Nasu-Nishimura Y, Sakaue F, Morishita Y, Okabe T, Ohwada S, Matsuura K, Akiyama T: PX-RICS mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex. Genes Dev. 2008, 22: 1244-1256. 10.1101/gad.1632308.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18451111" aria-label="PubMed reference 44">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXlslCqs70%3D" aria-label="CAS reference 44">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2335319" aria-label="PubMed Central reference 44">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 44" href="http://scholar.google.com/scholar_lookup?&title=PX-RICS%20mediates%20ER-to-Golgi%20transport%20of%20the%20N-cadherin%2Fbeta-catenin%20complex&journal=Genes%20Dev&doi=10.1101%2Fgad.1632308&volume=22&pages=1244-1256&publication_year=2008&author=Nakamura%2CT&author=Hayashi%2CT&author=Nasu-Nishimura%2CY&author=Sakaue%2CF&author=Morishita%2CY&author=Okabe%2CT&author=Ohwada%2CS&author=Matsuura%2CK&author=Akiyama%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="45."><p class="c-article-references__text" id="ref-CR45">Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ: The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Mol Cell Neurosci. 2001, 18: 13-25. 10.1006/mcne.2001.1005.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11461150" aria-label="PubMed reference 45">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3MXlt1Cmurs%3D" aria-label="CAS reference 45">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 45" href="http://scholar.google.com/scholar_lookup?&title=The%20subcellular%20distribution%20of%20GABARAP%20and%20its%20ability%20to%20interact%20with%20NSF%20suggest%20a%20role%20for%20this%20protein%20in%20the%20intracellular%20transport%20of%20GABA%28A%29%20receptors&journal=Mol%20Cell%20Neurosci&doi=10.1006%2Fmcne.2001.1005&volume=18&pages=13-25&publication_year=2001&author=Kittler%2CJT&author=Rostaing%2CP&author=Schiavo%2CG&author=Fritschy%2CJM&author=Olsen%2CR&author=Triller%2CA&author=Moss%2CSJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="46."><p class="c-article-references__text" id="ref-CR46">Chen L, Wang H, Vicini S, Olsen RW: The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics. Proc Natl Acad Sci USA. 2000, 97: 11557-11562.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10984509" aria-label="PubMed reference 46">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXnsF2qsLk%3D" aria-label="CAS reference 46">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC17239" aria-label="PubMed Central reference 46">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 46" href="http://scholar.google.com/scholar_lookup?&title=The%20gamma-aminobutyric%20acid%20type%20A%20%28GABAA%29%20receptor-associated%20protein%20%28GABARAP%29%20promotes%20GABAA%20receptor%20clustering%20and%20modulates%20the%20channel%20kinetics&journal=Proc%20Natl%20Acad%20Sci%20USA&volume=97&pages=11557-11562&publication_year=2000&author=Chen%2CL&author=Wang%2CH&author=Vicini%2CS&author=Olsen%2CRW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="47."><p class="c-article-references__text" id="ref-CR47">Wang H, Olsen RW: Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction. J Neurochem. 2000, 75: 644-655.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10899939" aria-label="PubMed reference 47">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXltFCltL4%3D" aria-label="CAS reference 47">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 47" href="http://scholar.google.com/scholar_lookup?&title=Binding%20of%20the%20GABA%28A%29%20receptor-associated%20protein%20%28GABARAP%29%20to%20microtubules%20and%20microfilaments%20suggests%20involvement%20of%20the%20cytoskeleton%20in%20GABARAPGABA%28A%29%20receptor%20interaction&journal=J%20Neurochem&volume=75&pages=644-655&publication_year=2000&author=Wang%2CH&author=Olsen%2CRW"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="48."><p class="c-article-references__text" id="ref-CR48">Chen C, Li JG, Chen Y, Huang P, Wang Y, Liu-Chen LY: GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor. J Biol Chem. 2006, 281: 7983-7993. 10.1074/jbc.M509805200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16431922" aria-label="PubMed reference 48">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28Xitl2ku74%3D" aria-label="CAS reference 48">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 48" href="http://scholar.google.com/scholar_lookup?&title=GEC1%20interacts%20with%20the%20kappa%20opioid%20receptor%20and%20enhances%20expression%20of%20the%20receptor&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M509805200&volume=281&pages=7983-7993&publication_year=2006&author=Chen%2CC&author=Li%2CJG&author=Chen%2CY&author=Huang%2CP&author=Wang%2CY&author=Liu-Chen%2CLY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="49."><p class="c-article-references__text" id="ref-CR49">Mansuy V, Boireau W, Fraichard A, Schlick JL, Jouvenot M, Delage-Mourroux R: GEC1, a protein related to GABARAP, interacts with tubulin and GABA(A) receptor. Biochem Biophys Res Commun. 2004, 325: 639-648. 10.1016/j.bbrc.2004.10.072.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15530441" aria-label="PubMed reference 49">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXpsVOlsbc%3D" aria-label="CAS reference 49">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 49" href="http://scholar.google.com/scholar_lookup?&title=GEC1%2C%20a%20protein%20related%20to%20GABARAP%2C%20interacts%20with%20tubulin%20and%20GABA%28A%29%20receptor&journal=Biochem%20Biophys%20Res%20Commun&doi=10.1016%2Fj.bbrc.2004.10.072&volume=325&pages=639-648&publication_year=2004&author=Mansuy%2CV&author=Boireau%2CW&author=Fraichard%2CA&author=Schlick%2CJL&author=Jouvenot%2CM&author=Delage-Mourroux%2CR"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="50."><p class="c-article-references__text" id="ref-CR50">Chen C, Wang Y, Huang P, Liu-Chen LY: Effects of C-terminal modifications of GEC1 Protein and {gamma}-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP), two microtubule-associated proteins, on {kappa} opioid receptor expression. J Biol Chem. 2011, 286: 15106-15115. 10.1074/jbc.M111.230896.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21388957" aria-label="PubMed reference 50">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXltVSqtb8%3D" aria-label="CAS reference 50">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083202" aria-label="PubMed Central reference 50">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 50" href="http://scholar.google.com/scholar_lookup?&title=Effects%20of%20C-terminal%20modifications%20of%20GEC1%20Protein%20and%20%7Bgamma%7D-aminobutyric%20acid%20type%20A%20%28GABAA%29%20receptor-associated%20protein%20%28GABARAP%29%2C%20two%20microtubule-associated%20proteins%2C%20on%20%7Bkappa%7D%20opioid%20receptor%20expression&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M111.230896&volume=286&pages=15106-15115&publication_year=2011&author=Chen%2CC&author=Wang%2CY&author=Huang%2CP&author=Liu-Chen%2CLY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="51."><p class="c-article-references__text" id="ref-CR51">Chen Y, Chen C, Kotsikorou E, Lynch DL, Reggio PH, Liu-Chen LY: GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect. J Biol Chem. 2009, 284: 1673-1685.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19001416" aria-label="PubMed reference 51">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXjtFOitQ%3D%3D" aria-label="CAS reference 51">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615498" aria-label="PubMed Central reference 51">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 51" href="http://scholar.google.com/scholar_lookup?&title=GEC1-kappa%20opioid%20receptor%20binding%20involves%20hydrophobic%20interactions%3A%20GEC1%20has%20chaperone-like%20effect&journal=J%20Biol%20Chem&volume=284&pages=1673-1685&publication_year=2009&author=Chen%2CY&author=Chen%2CC&author=Kotsikorou%2CE&author=Lynch%2CDL&author=Reggio%2CPH&author=Liu-Chen%2CLY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="52."><p class="c-article-references__text" id="ref-CR52">Tamura N, Oku M, Sakai Y: Atg8 regulates vacuolar membrane dynamics in a lipidation-independent manner in <i>Pichia pastoris</i>. J Cell Sci. 2010, 123: 4107-4116. 10.1242/jcs.070045.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21045113" aria-label="PubMed reference 52">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXktFKqsw%3D%3D" aria-label="CAS reference 52">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 52" href="http://scholar.google.com/scholar_lookup?&title=Atg8%20regulates%20vacuolar%20membrane%20dynamics%20in%20a%20lipidation-independent%20manner%20in%20Pichia%20pastoris&journal=J%20Cell%20Sci&doi=10.1242%2Fjcs.070045&volume=123&pages=4107-4116&publication_year=2010&author=Tamura%2CN&author=Oku%2CM&author=Sakai%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="53."><p class="c-article-references__text" id="ref-CR53">Legesse-Miller A, Sagiv Y, Glozman R, Elazar Z: Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. J Biol Chem. 2000, 275: 32966-32973.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10837468" aria-label="PubMed reference 53">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXnslOhsrY%3D" aria-label="CAS reference 53">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 53" href="http://scholar.google.com/scholar_lookup?&title=Aut7p%2C%20a%20soluble%20autophagic%20factor%2C%20participates%20in%20multiple%20membrane%20trafficking%20processes&journal=J%20Biol%20Chem&volume=275&pages=32966-32973&publication_year=2000&author=Legesse-Miller%2CA&author=Sagiv%2CY&author=Glozman%2CR&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="54."><p class="c-article-references__text" id="ref-CR54">Harding TM, Morano KA, Scott SV, Klionsky DJ: Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995, 131: 591-602. 10.1083/jcb.131.3.591.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=7593182" aria-label="PubMed reference 54">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK2MXovVKlu7g%3D" aria-label="CAS reference 54">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 54" href="http://scholar.google.com/scholar_lookup?&title=Isolation%20and%20characterization%20of%20yeast%20mutants%20in%20the%20cytoplasm%20to%20vacuole%20protein%20targeting%20pathway&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.131.3.591&volume=131&pages=591-602&publication_year=1995&author=Harding%2CTM&author=Morano%2CKA&author=Scott%2CSV&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="55."><p class="c-article-references__text" id="ref-CR55">Lang T, Schaeffeler E, Bernreuther D, Bredschneider M, Wolf DH, Thumm M: Aut2p and Aut7p, two novel microtubule-associated proteins are essential for delivery of autophagic vesicles to the vacuole. EMBO J. 1998, 17: 3597-3607. 10.1093/emboj/17.13.3597.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9649430" aria-label="PubMed reference 55">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1cXkslSjtrc%3D" aria-label="CAS reference 55">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170696" aria-label="PubMed Central reference 55">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 55" href="http://scholar.google.com/scholar_lookup?&title=Aut2p%20and%20Aut7p%2C%20two%20novel%20microtubule-associated%20proteins%20are%20essential%20for%20delivery%20of%20autophagic%20vesicles%20to%20the%20vacuole&journal=EMBO%20J&doi=10.1093%2Femboj%2F17.13.3597&volume=17&pages=3597-3607&publication_year=1998&author=Lang%2CT&author=Schaeffeler%2CE&author=Bernreuther%2CD&author=Bredschneider%2CM&author=Wolf%2CDH&author=Thumm%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="56."><p class="c-article-references__text" id="ref-CR56">Scott SV, Hefner-Gravink A, Morano KA, Noda T, Ohsumi Y, Klionsky DJ: Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole. Proc Natl Acad Sci USA. 1996, 93: 12304-12308. 10.1073/pnas.93.22.12304.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=8901576" aria-label="PubMed reference 56">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK28Xms1Gjt7s%3D" aria-label="CAS reference 56">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC37986" aria-label="PubMed Central reference 56">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 56" href="http://scholar.google.com/scholar_lookup?&title=Cytoplasm-to-vacuole%20targeting%20and%20autophagy%20employ%20the%20same%20machinery%20to%20deliver%20proteins%20to%20the%20yeast%20vacuole&journal=Proc%20Natl%20Acad%20Sci%20USA&doi=10.1073%2Fpnas.93.22.12304&volume=93&pages=12304-12308&publication_year=1996&author=Scott%2CSV&author=Hefner-Gravink%2CA&author=Morano%2CKA&author=Noda%2CT&author=Ohsumi%2CY&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="57."><p class="c-article-references__text" id="ref-CR57">Lynch-Day MA, Klionsky DJ: The Cvt pathway as a model for selective autophagy. FEBS Lett. 2010, 584: 1359-1366. 10.1016/j.febslet.2010.02.013.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20146925" aria-label="PubMed reference 57">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXjs12nu7c%3D" aria-label="CAS reference 57">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843786" aria-label="PubMed Central reference 57">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 57" href="http://scholar.google.com/scholar_lookup?&title=The%20Cvt%20pathway%20as%20a%20model%20for%20selective%20autophagy&journal=FEBS%20Lett&doi=10.1016%2Fj.febslet.2010.02.013&volume=584&pages=1359-1366&publication_year=2010&author=Lynch-Day%2CMA&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="58."><p class="c-article-references__text" id="ref-CR58">Suzuki K, Kondo C, Morimoto M, Ohsumi Y: Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p. J Biol Chem. 2010, 285: 30019-30025. 10.1074/jbc.M110.143511.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20639194" aria-label="PubMed reference 58">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtFKksL%2FP" aria-label="CAS reference 58">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943286" aria-label="PubMed Central reference 58">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 58" href="http://scholar.google.com/scholar_lookup?&title=Selective%20transport%20of%20alpha-mannosidase%20by%20autophagic%20pathways%3A%20identification%20of%20a%20novel%20receptor%2C%20Atg34p&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M110.143511&volume=285&pages=30019-30025&publication_year=2010&author=Suzuki%2CK&author=Kondo%2CC&author=Morimoto%2CM&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="59."><p class="c-article-references__text" id="ref-CR59">Huang WP, Scott SV, Kim J, Klionsky DJ: The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem. 2000, 275: 5845-5851. 10.1074/jbc.275.8.5845.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10681575" aria-label="PubMed reference 59">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXhsFKkurw%3D" aria-label="CAS reference 59">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 59" href="http://scholar.google.com/scholar_lookup?&title=The%20itinerary%20of%20a%20vesicle%20component%2C%20Aut7p%2FCvt5p%2C%20terminates%20in%20the%20yeast%20vacuole%20via%20the%20autophagy%2FCvt%20pathways&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.275.8.5845&volume=275&pages=5845-5851&publication_year=2000&author=Huang%2CWP&author=Scott%2CSV&author=Kim%2CJ&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="60."><p class="c-article-references__text" id="ref-CR60">Kim J, Huang WP, Klionsky DJ: Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001, 152: 51-64. 10.1083/jcb.152.1.51.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11149920" aria-label="PubMed reference 60">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3MXjslyisA%3D%3D" aria-label="CAS reference 60">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193654" aria-label="PubMed Central reference 60">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 60" href="http://scholar.google.com/scholar_lookup?&title=Membrane%20recruitment%20of%20Aut7p%20in%20the%20autophagy%20and%20cytoplasm%20to%20vacuole%20targeting%20pathways%20requires%20Aut1p%2C%20Aut2p%2C%20and%20the%20autophagy%20conjugation%20complex&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.152.1.51&volume=152&pages=51-64&publication_year=2001&author=Kim%2CJ&author=Huang%2CWP&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="61."><p class="c-article-references__text" id="ref-CR61">Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, Ohsumi M, Takao T, Noda T, Ohsumi Y: The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 2000, 151: 263-276. 10.1083/jcb.151.2.263.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11038174" aria-label="PubMed reference 61">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXnsVaqs7c%3D" aria-label="CAS reference 61">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192639" aria-label="PubMed Central reference 61">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 61" href="http://scholar.google.com/scholar_lookup?&title=The%20reversible%20modification%20regulates%20the%20membrane-binding%20state%20of%20Apg8%2FAut7%20essential%20for%20autophagy%20and%20the%20cytoplasm%20to%20vacuole%20targeting%20pathway&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.151.2.263&volume=151&pages=263-276&publication_year=2000&author=Kirisako%2CT&author=Ichimura%2CY&author=Okada%2CH&author=Kabeya%2CY&author=Mizushima%2CN&author=Yoshimori%2CT&author=Ohsumi%2CM&author=Takao%2CT&author=Noda%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="62."><p class="c-article-references__text" id="ref-CR62">Tanida I, Mizushima N, Kiyooka M, Ohsumi M, Ueno T, Ohsumi Y, Kominami E: Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy. Mol Biol Cell. 1999, 10: 1367-1379.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10233150" aria-label="PubMed reference 62">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK1MXjsFSitrc%3D" aria-label="CAS reference 62">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC25280" aria-label="PubMed Central reference 62">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 62" href="http://scholar.google.com/scholar_lookup?&title=Apg7p%2FCvt2p%3A%20A%20novel%20protein-activating%20enzyme%20essential%20for%20autophagy&journal=Mol%20Biol%20Cell&volume=10&pages=1367-1379&publication_year=1999&author=Tanida%2CI&author=Mizushima%2CN&author=Kiyooka%2CM&author=Ohsumi%2CM&author=Ueno%2CT&author=Ohsumi%2CY&author=Kominami%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="63."><p class="c-article-references__text" id="ref-CR63">Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M: AUT1, a gene essential for autophagocytosis in the yeast <i>Saccharomyces cerevisiae</i>. J Bacteriol. 1997, 179: 1068-1076.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9023185" aria-label="PubMed reference 63">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK2sXhtFKru7g%3D" aria-label="CAS reference 63">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC178799" aria-label="PubMed Central reference 63">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 63" href="http://scholar.google.com/scholar_lookup?&title=AUT1%2C%20a%20gene%20essential%20for%20autophagocytosis%20in%20the%20yeast%20Saccharomyces%20cerevisiae&journal=J%20Bacteriol&volume=179&pages=1068-1076&publication_year=1997&author=Schlumpberger%2CM&author=Schaeffeler%2CE&author=Straub%2CM&author=Bredschneider%2CM&author=Wolf%2CDH&author=Thumm%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="64."><p class="c-article-references__text" id="ref-CR64">Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y: A ubiquitin-like system mediates protein lipidation. Nature. 2000, 408: 488-492. 10.1038/35044114.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11100732" aria-label="PubMed reference 64">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXos1Srtrk%3D" aria-label="CAS reference 64">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 64" href="http://scholar.google.com/scholar_lookup?&title=A%20ubiquitin-like%20system%20mediates%20protein%20lipidation&journal=Nature&doi=10.1038%2F35044114&volume=408&pages=488-492&publication_year=2000&author=Ichimura%2CY&author=Kirisako%2CT&author=Takao%2CT&author=Satomi%2CY&author=Shimonishi%2CY&author=Ishihara%2CN&author=Mizushima%2CN&author=Tanida%2CI&author=Kominami%2CE&author=Ohsumi%2CM&author=Noda%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="65."><p class="c-article-references__text" id="ref-CR65">Suzuki K, Ohsumi Y: Current knowledge of the pre-autophagosomal structure (PAS). FEBS Lett. 2010, 584: 1280-1286. 10.1016/j.febslet.2010.02.001.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20138172" aria-label="PubMed reference 65">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXjs12nurc%3D" aria-label="CAS reference 65">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 65" href="http://scholar.google.com/scholar_lookup?&title=Current%20knowledge%20of%20the%20pre-autophagosomal%20structure%20%28PAS%29&journal=FEBS%20Lett&doi=10.1016%2Fj.febslet.2010.02.001&volume=584&pages=1280-1286&publication_year=2010&author=Suzuki%2CK&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="66."><p class="c-article-references__text" id="ref-CR66">Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y: The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001, 20: 5971-5981. 10.1093/emboj/20.21.5971.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11689437" aria-label="PubMed reference 66">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3MXovVSit7k%3D" aria-label="CAS reference 66">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC125692" aria-label="PubMed Central reference 66">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 66" href="http://scholar.google.com/scholar_lookup?&title=The%20pre-autophagosomal%20structure%20organized%20by%20concerted%20functions%20of%20APG%20genes%20is%20essential%20for%20autophagosome%20formation&journal=EMBO%20J&doi=10.1093%2Femboj%2F20.21.5971&volume=20&pages=5971-5981&publication_year=2001&author=Suzuki%2CK&author=Kirisako%2CT&author=Kamada%2CY&author=Mizushima%2CN&author=Noda%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="67."><p class="c-article-references__text" id="ref-CR67">Hanada T, Noda NN, Satomi Y, Ichimura Y, Fujioka Y, Takao T, Inagaki F, Ohsumi Y: The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem. 2007, 282: 37298-37302. 10.1074/jbc.C700195200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17986448" aria-label="PubMed reference 67">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhsVGjtr7F" aria-label="CAS reference 67">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 67" href="http://scholar.google.com/scholar_lookup?&title=The%20Atg12-Atg5%20conjugate%20has%20a%20novel%20E3-like%20activity%20for%20protein%20lipidation%20in%20autophagy&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.C700195200&volume=282&pages=37298-37302&publication_year=2007&author=Hanada%2CT&author=Noda%2CNN&author=Satomi%2CY&author=Ichimura%2CY&author=Fujioka%2CY&author=Takao%2CT&author=Inagaki%2CF&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="68."><p class="c-article-references__text" id="ref-CR68">Abeliovich H, Dunn WA, Kim J, Klionsky DJ: Dissection of autophagosome biogenesis into distinct nucleation and expansion steps. J Cell Biol. 2000, 151: 1025-1034. 10.1083/jcb.151.5.1025.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11086004" aria-label="PubMed reference 68">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXovVyks70%3D" aria-label="CAS reference 68">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174351" aria-label="PubMed Central reference 68">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 68" href="http://scholar.google.com/scholar_lookup?&title=Dissection%20of%20autophagosome%20biogenesis%20into%20distinct%20nucleation%20and%20expansion%20steps&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.151.5.1025&volume=151&pages=1025-1034&publication_year=2000&author=Abeliovich%2CH&author=Dunn%2CWA&author=Kim%2CJ&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="69."><p class="c-article-references__text" id="ref-CR69">Xie Z, Nair U, Klionsky DJ: Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell. 2008, 19: 3290-3298. 10.1091/mbc.E07-12-1292.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18508918" aria-label="PubMed reference 69">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXpvV2hsr0%3D" aria-label="CAS reference 69">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488302" aria-label="PubMed Central reference 69">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 69" href="http://scholar.google.com/scholar_lookup?&title=Atg8%20controls%20phagophore%20expansion%20during%20autophagosome%20formation&journal=Mol%20Biol%20Cell&doi=10.1091%2Fmbc.E07-12-1292&volume=19&pages=3290-3298&publication_year=2008&author=Xie%2CZ&author=Nair%2CU&author=Klionsky%2CDJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="70."><p class="c-article-references__text" id="ref-CR70">Amar N, Lustig G, Ichimura Y, Ohsumi Y, Elazar Z: Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy. EMBO Rep. 2006, 7: 635-642.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16680092" aria-label="PubMed reference 70">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD28Xlt1agsr4%3D" aria-label="CAS reference 70">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479593" aria-label="PubMed Central reference 70">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 70" href="http://scholar.google.com/scholar_lookup?&title=Two%20newly%20identified%20sites%20in%20the%20ubiquitin-like%20protein%20Atg8%20are%20essential%20for%20autophagy&journal=EMBO%20Rep&volume=7&pages=635-642&publication_year=2006&author=Amar%2CN&author=Lustig%2CG&author=Ichimura%2CY&author=Ohsumi%2CY&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="71."><p class="c-article-references__text" id="ref-CR71">Ho KH, Chang HE, Huang WP: Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function. Autophagy. 2009, 5: 461-471. 10.4161/auto.5.4.7696.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19398890" aria-label="PubMed reference 71">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXnvVyrsLw%3D" aria-label="CAS reference 71">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 71" href="http://scholar.google.com/scholar_lookup?&title=Mutation%20at%20the%20cargo-receptor%20binding%20site%20of%20Atg8%20also%20affects%20its%20general%20autophagy%20regulation%20function&journal=Autophagy&doi=10.4161%2Fauto.5.4.7696&volume=5&pages=461-471&publication_year=2009&author=Ho%2CKH&author=Chang%2CHE&author=Huang%2CWP"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="72."><p class="c-article-references__text" id="ref-CR72">Krick R, Bremer S, Welter E, Schlotterhose P, Muehe Y, Eskelinen EL, Thumm M: Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J Cell Biol. 2010, 190: 965-973. 10.1083/jcb.201002075.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20855502" aria-label="PubMed reference 72">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXht1ahsbjN" aria-label="CAS reference 72">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101598" aria-label="PubMed Central reference 72">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 72" href="http://scholar.google.com/scholar_lookup?&title=Cdc48%2Fp97%20and%20Shp1%2Fp47%20regulate%20autophagosome%20biogenesis%20in%20concert%20with%20ubiquitin-like%20Atg8&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.201002075&volume=190&pages=965-973&publication_year=2010&author=Krick%2CR&author=Bremer%2CS&author=Welter%2CE&author=Schlotterhose%2CP&author=Muehe%2CY&author=Eskelinen%2CEL&author=Thumm%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="73."><p class="c-article-references__text" id="ref-CR73">Chakrama FZ, Seguin-Py S, Le Grand JN, Fraichard A, Delage-Mourroux R, Despouy G, Perez V, Jouvenot M, Boyer-Guittaut M: GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy. 2010</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 73" href="http://scholar.google.com/scholar_lookup?&title=GABARAPL1%20%28GEC1%29%20associates%20with%20autophagic%20vesicles&publication_year=2010&author=Chakrama%2CFZ&author=Seguin-Py%2CS&author=Le%20Grand%2CJN&author=Fraichard%2CA&author=Delage-Mourroux%2CR&author=Despouy%2CG&author=Perez%2CV&author=Jouvenot%2CM&author=Boyer-Guittaut%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="74."><p class="c-article-references__text" id="ref-CR74">Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19: 5720-5728. 10.1093/emboj/19.21.5720.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=11060023" aria-label="PubMed reference 74">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3cXovFaiurk%3D" aria-label="CAS reference 74">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC305793" aria-label="PubMed Central reference 74">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 74" href="http://scholar.google.com/scholar_lookup?&title=LC3%2C%20a%20mammalian%20homologue%20of%20yeast%20Apg8p%2C%20is%20localized%20in%20autophagosome%20membranes%20after%20processing&journal=EMBO%20J&doi=10.1093%2Femboj%2F19.21.5720&volume=19&pages=5720-5728&publication_year=2000&author=Kabeya%2CY&author=Mizushima%2CN&author=Ueno%2CT&author=Yamamoto%2CA&author=Kirisako%2CT&author=Noda%2CT&author=Kominami%2CE&author=Ohsumi%2CY&author=Yoshimori%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="75."><p class="c-article-references__text" id="ref-CR75">Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T: LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004, 117: 2805-2812. 10.1242/jcs.01131.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15169837" aria-label="PubMed reference 75">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXlvFehtL4%3D" aria-label="CAS reference 75">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 75" href="http://scholar.google.com/scholar_lookup?&title=LC3%2C%20GABARAP%20and%20GATE16%20localize%20to%20autophagosomal%20membrane%20depending%20on%20form-II%20formation&journal=J%20Cell%20Sci&doi=10.1242%2Fjcs.01131&volume=117&pages=2805-2812&publication_year=2004&author=Kabeya%2CY&author=Mizushima%2CN&author=Yamamoto%2CA&author=Oshitani-Okamoto%2CS&author=Ohsumi%2CY&author=Yoshimori%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="76."><p class="c-article-references__text" id="ref-CR76">Tanida I, Ueno T, Kominami E: LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004, 36: 2503-2518. 10.1016/j.biocel.2004.05.009.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15325588" aria-label="PubMed reference 76">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXmvFemu7Y%3D" aria-label="CAS reference 76">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 76" href="http://scholar.google.com/scholar_lookup?&title=LC3%20conjugation%20system%20in%20mammalian%20autophagy&journal=Int%20J%20Biochem%20Cell%20Biol&doi=10.1016%2Fj.biocel.2004.05.009&volume=36&pages=2503-2518&publication_year=2004&author=Tanida%2CI&author=Ueno%2CT&author=Kominami%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="77."><p class="c-article-references__text" id="ref-CR77">Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T: The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell. 2008, 19: 2092-2100. 10.1091/mbc.E07-12-1257.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18321988" aria-label="PubMed reference 77">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXlslelsL0%3D" aria-label="CAS reference 77">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366860" aria-label="PubMed Central reference 77">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 77" href="http://scholar.google.com/scholar_lookup?&title=The%20Atg16L%20complex%20specifies%20the%20site%20of%20LC3%20lipidation%20for%20membrane%20biogenesis%20in%20autophagy&journal=Mol%20Biol%20Cell&doi=10.1091%2Fmbc.E07-12-1257&volume=19&pages=2092-2100&publication_year=2008&author=Fujita%2CN&author=Itoh%2CT&author=Omori%2CH&author=Fukuda%2CM&author=Noda%2CT&author=Yoshimori%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="78."><p class="c-article-references__text" id="ref-CR78">Hemelaar J, Lelyveld VS, Kessler BM, Ploegh HL: A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J Biol Chem. 2003, 278: 51841-51850. 10.1074/jbc.M308762200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14530254" aria-label="PubMed reference 78">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXpslOgtLc%3D" aria-label="CAS reference 78">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 78" href="http://scholar.google.com/scholar_lookup?&title=A%20single%20protease%2C%20Apg4B%2C%20is%20specific%20for%20the%20autophagy-related%20ubiquitin-like%20proteins%20GATE-16%2C%20MAP1-LC3%2C%20GABARAP%2C%20and%20Apg8L&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M308762200&volume=278&pages=51841-51850&publication_year=2003&author=Hemelaar%2CJ&author=Lelyveld%2CVS&author=Kessler%2CBM&author=Ploegh%2CHL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="79."><p class="c-article-references__text" id="ref-CR79">Tanida I, Ueno T, Kominami E: Human light chain 3/MAP1LC3B is cleaved at its carboxyl-terminal Met121 to expose Gly120 for lipidation and targeting to autophagosomal membranes. J Biol Chem. 2004, 279: 47704-47710. 10.1074/jbc.M407016200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15355958" aria-label="PubMed reference 79">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXptl2gu70%3D" aria-label="CAS reference 79">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 79" href="http://scholar.google.com/scholar_lookup?&title=Human%20light%20chain%203%2FMAP1LC3B%20is%20cleaved%20at%20its%20carboxyl-terminal%20Met121%20to%20expose%20Gly120%20for%20lipidation%20and%20targeting%20to%20autophagosomal%20membranes&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M407016200&volume=279&pages=47704-47710&publication_year=2004&author=Tanida%2CI&author=Ueno%2CT&author=Kominami%2CE"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="80."><p class="c-article-references__text" id="ref-CR80">Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM: Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J Biol Chem. 2011, 286: 7327-7338. 10.1074/jbc.M110.199059.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21177865" aria-label="PubMed reference 80">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXisVyqsLs%3D" aria-label="CAS reference 80">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044989" aria-label="PubMed Central reference 80">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 80" href="http://scholar.google.com/scholar_lookup?&title=Kinetics%20comparisons%20of%20mammalian%20Atg4%20homologues%20indicate%20selective%20preferences%20toward%20diverse%20Atg8%20substrates&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M110.199059&volume=286&pages=7327-7338&publication_year=2011&author=Li%2CM&author=Hou%2CY&author=Wang%2CJ&author=Chen%2CX&author=Shao%2CZM&author=Yin%2CXM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="81."><p class="c-article-references__text" id="ref-CR81">Scherz-Shouval R, Sagiv Y, Shorer H, Elazar Z: The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A. J Biol Chem. 2003, 278: 14053-14058. 10.1074/jbc.M212108200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12473658" aria-label="PubMed reference 81">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD3sXjtVSiurc%3D" aria-label="CAS reference 81">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 81" href="http://scholar.google.com/scholar_lookup?&title=The%20COOH%20terminus%20of%20GATE-16%2C%20an%20intra-Golgi%20transport%20modulator%2C%20is%20cleaved%20by%20the%20human%20cysteine%20protease%20HsApg4A&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M212108200&volume=278&pages=14053-14058&publication_year=2003&author=Scherz-Shouval%2CR&author=Sagiv%2CY&author=Shorer%2CH&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="82."><p class="c-article-references__text" id="ref-CR82">Betin VM, Lane JD: Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. J Cell Sci. 2009, 122: 2554-2566. 10.1242/jcs.046250.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19549685" aria-label="PubMed reference 82">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXpvFGlsrs%3D" aria-label="CAS reference 82">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704886" aria-label="PubMed Central reference 82">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 82" href="http://scholar.google.com/scholar_lookup?&title=Caspase%20cleavage%20of%20Atg4D%20stimulates%20GABARAP-L1%20processing%20and%20triggers%20mitochondrial%20targeting%20and%20apoptosis&journal=J%20Cell%20Sci&doi=10.1242%2Fjcs.046250&volume=122&pages=2554-2566&publication_year=2009&author=Betin%2CVM&author=Lane%2CJD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="83."><p class="c-article-references__text" id="ref-CR83">Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z: Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 2007, 26: 1749-1760. 10.1038/sj.emboj.7601623.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17347651" aria-label="PubMed reference 83">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXjslOmtLs%3D" aria-label="CAS reference 83">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847657" aria-label="PubMed Central reference 83">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 83" href="http://scholar.google.com/scholar_lookup?&title=Reactive%20oxygen%20species%20are%20essential%20for%20autophagy%20and%20specifically%20regulate%20the%20activity%20of%20Atg4&journal=EMBO%20J&doi=10.1038%2Fsj.emboj.7601623&volume=26&pages=1749-1760&publication_year=2007&author=Scherz-Shouval%2CR&author=Shvets%2CE&author=Fass%2CE&author=Shorer%2CH&author=Gil%2CL&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="84."><p class="c-article-references__text" id="ref-CR84">Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y: <i>In vivo</i> analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004, 15: 1101-1111.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14699058" aria-label="PubMed reference 84">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2cXitlGhu7g%3D" aria-label="CAS reference 84">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC363084" aria-label="PubMed Central reference 84">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 84" href="http://scholar.google.com/scholar_lookup?&title=In%20vivo%20analysis%20of%20autophagy%20in%20response%20to%20nutrient%20starvation%20using%20transgenic%20mice%20expressing%20a%20fluorescent%20autophagosome%20marker&journal=Mol%20Biol%20Cell&volume=15&pages=1101-1111&publication_year=2004&author=Mizushima%2CN&author=Yamamoto%2CA&author=Matsui%2CM&author=Yoshimori%2CT&author=Ohsumi%2CY"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="85."><p class="c-article-references__text" id="ref-CR85">Tanida I, Waguri S: Measurement of autophagy in cells and tissues. Methods Mol Biol. 2010, 648: 193-214. 10.1007/978-1-60761-756-3_13.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20700714" aria-label="PubMed reference 85">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXht1SmsLnF" aria-label="CAS reference 85">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 85" href="http://scholar.google.com/scholar_lookup?&title=Measurement%20of%20autophagy%20in%20cells%20and%20tissues&journal=Methods%20Mol%20Biol&doi=10.1007%2F978-1-60761-756-3_13&volume=648&pages=193-214&publication_year=2010&author=Tanida%2CI&author=Waguri%2CS"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="86."><p class="c-article-references__text" id="ref-CR86">Fujita N, Hayashi-Nishino M, Fukumoto H, Omori H, Yamamoto A, Noda T, Yoshimori T: An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure. Mol Biol Cell. 2008, 19: 4651-4659. 10.1091/mbc.E08-03-0312.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18768752" aria-label="PubMed reference 86">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXhtlKqsbbJ" aria-label="CAS reference 86">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575160" aria-label="PubMed Central reference 86">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 86" href="http://scholar.google.com/scholar_lookup?&title=An%20Atg4B%20mutant%20hampers%20the%20lipidation%20of%20LC3%20paralogues%20and%20causes%20defects%20in%20autophagosome%20closure&journal=Mol%20Biol%20Cell&doi=10.1091%2Fmbc.E08-03-0312&volume=19&pages=4651-4659&publication_year=2008&author=Fujita%2CN&author=Hayashi-Nishino%2CM&author=Fukumoto%2CH&author=Omori%2CH&author=Yamamoto%2CA&author=Noda%2CT&author=Yoshimori%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="87."><p class="c-article-references__text" id="ref-CR87">Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T, Yamamoto A: A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol. 2009, 11: 1433-1437. 10.1038/ncb1991.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19898463" aria-label="PubMed reference 87">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhsV2gsLnE" aria-label="CAS reference 87">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 87" href="http://scholar.google.com/scholar_lookup?&title=A%20subdomain%20of%20the%20endoplasmic%20reticulum%20forms%20a%20cradle%20for%20autophagosome%20formation&journal=Nat%20Cell%20Biol&doi=10.1038%2Fncb1991&volume=11&pages=1433-1437&publication_year=2009&author=Hayashi-Nishino%2CM&author=Fujita%2CN&author=Noda%2CT&author=Yamaguchi%2CA&author=Yoshimori%2CT&author=Yamamoto%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="88."><p class="c-article-references__text" id="ref-CR88">Sou YS, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T, Sawada N, Yamada A, Mizushima N, Uchiyama Y, Kominami E, Tanaka K, Komatsu M: The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell. 2008, 19: 4762-4775. 10.1091/mbc.E08-03-0309.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18768753" aria-label="PubMed reference 88">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXhtlKqsbfJ" aria-label="CAS reference 88">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575156" aria-label="PubMed Central reference 88">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 88" href="http://scholar.google.com/scholar_lookup?&title=The%20Atg8%20conjugation%20system%20is%20indispensable%20for%20proper%20development%20of%20autophagic%20isolation%20membranes%20in%20mice&journal=Mol%20Biol%20Cell&doi=10.1091%2Fmbc.E08-03-0309&volume=19&pages=4762-4775&publication_year=2008&author=Sou%2CYS&author=Waguri%2CS&author=Iwata%2CJ&author=Ueno%2CT&author=Fujimura%2CT&author=Hara%2CT&author=Sawada%2CN&author=Yamada%2CA&author=Mizushima%2CN&author=Uchiyama%2CY&author=Kominami%2CE&author=Tanaka%2CK&author=Komatsu%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="89."><p class="c-article-references__text" id="ref-CR89">Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z: LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 2010, 29: 1792-1802. 10.1038/emboj.2010.74.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20418806" aria-label="PubMed reference 89">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXkvFSjs74%3D" aria-label="CAS reference 89">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885923" aria-label="PubMed Central reference 89">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 89" href="http://scholar.google.com/scholar_lookup?&title=LC3%20and%20GATE-16%2FGABARAP%20subfamilies%20are%20both%20essential%20yet%20act%20differently%20in%20autophagosome%20biogenesis&journal=EMBO%20J&doi=10.1038%2Femboj.2010.74&volume=29&pages=1792-1802&publication_year=2010&author=Weidberg%2CH&author=Shvets%2CE&author=Shpilka%2CT&author=Shimron%2CF&author=Shinder%2CV&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="90."><p class="c-article-references__text" id="ref-CR90">Mauvezin C, Orpinell M, Francis VA, Mansilla F, Duran J, Ribas V, Palacin M, Boya P, Teleman AA, Zorzano A: The nuclear cofactor DOR regulates autophagy in mammalian and <i>Drosophila</i> cells. EMBO Rep. 2010, 11: 37-44. 10.1038/embor.2009.242.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20010805" aria-label="PubMed reference 90">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhsFChtbbO" aria-label="CAS reference 90">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816618" aria-label="PubMed Central reference 90">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 90" href="http://scholar.google.com/scholar_lookup?&title=The%20nuclear%20cofactor%20DOR%20regulates%20autophagy%20in%20mammalian%20and%20Drosophila%20cells&journal=EMBO%20Rep&doi=10.1038%2Fembor.2009.242&volume=11&pages=37-44&publication_year=2010&author=Mauvezin%2CC&author=Orpinell%2CM&author=Francis%2CVA&author=Mansilla%2CF&author=Duran%2CJ&author=Ribas%2CV&author=Palacin%2CM&author=Boya%2CP&author=Teleman%2CAA&author=Zorzano%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="91."><p class="c-article-references__text" id="ref-CR91">Nowak J, Archange C, Tardivel-Lacombe J, Pontarotti P, Pebusque MJ, Vaccaro MI, Velasco G, Dagorn JC, Iovanna JL: The TP53INP2 protein is required for autophagy in mammalian cells. Mol Biol Cell. 2009, 20: 870-881.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19056683" aria-label="PubMed reference 91">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXisVSnsLo%3D" aria-label="CAS reference 91">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633384" aria-label="PubMed Central reference 91">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 91" href="http://scholar.google.com/scholar_lookup?&title=The%20TP53INP2%20protein%20is%20required%20for%20autophagy%20in%20mammalian%20cells&journal=Mol%20Biol%20Cell&volume=20&pages=870-881&publication_year=2009&author=Nowak%2CJ&author=Archange%2CC&author=Tardivel-Lacombe%2CJ&author=Pontarotti%2CP&author=Pebusque%2CMJ&author=Vaccaro%2CMI&author=Velasco%2CG&author=Dagorn%2CJC&author=Iovanna%2CJL"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="92."><p class="c-article-references__text" id="ref-CR92">Lee IH, Finkel T: Regulation of autophagy by the p300 acetyltransferase. J Biol Chem. 2009, 284: 6322-6328.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19124466" aria-label="PubMed reference 92">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXisVSkurk%3D" aria-label="CAS reference 92">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 92" href="http://scholar.google.com/scholar_lookup?&title=Regulation%20of%20autophagy%20by%20the%20p300%20acetyltransferase&journal=J%20Biol%20Chem&volume=284&pages=6322-6328&publication_year=2009&author=Lee%2CIH&author=Finkel%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="93."><p class="c-article-references__text" id="ref-CR93">Cherra SJ, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, Day BW, Chu CT: Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol. 2010, 190: 533-539. 10.1083/jcb.201002108.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20713600" aria-label="PubMed reference 93">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtFajtb3O" aria-label="CAS reference 93">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928022" aria-label="PubMed Central reference 93">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 93" href="http://scholar.google.com/scholar_lookup?&title=Regulation%20of%20the%20autophagy%20protein%20LC3%20by%20phosphorylation&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.201002108&volume=190&pages=533-539&publication_year=2010&author=Cherra%2CSJ&author=Kulich%2CSM&author=Uechi%2CG&author=Balasubramani%2CM&author=Mountzouris%2CJ&author=Day%2CBW&author=Chu%2CCT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="94."><p class="c-article-references__text" id="ref-CR94">Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T: p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005, 171: 603-614. 10.1083/jcb.200507002.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16286508" aria-label="PubMed reference 94">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171557" aria-label="PubMed Central reference 94">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 94" href="http://scholar.google.com/scholar_lookup?&title=p62%2FSQSTM1%20forms%20protein%20aggregates%20degraded%20by%20autophagy%20and%20has%20a%20protective%20effect%20on%20huntingtin-induced%20cell%20death&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.200507002&volume=171&pages=603-614&publication_year=2005&author=Bjorkoy%2CG&author=Lamark%2CT&author=Brech%2CA&author=Outzen%2CH&author=Perander%2CM&author=Overvatn%2CA&author=Stenmark%2CH&author=Johansen%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="95."><p class="c-article-references__text" id="ref-CR95">Kirkin V, Lamark T, Sou YS, Bjørkøy G, Nunn JL, Bruun JA, Shvets E, McEwan DG, Clausen TH, Wild P, Bilusic I, Theurillat JP, Øvervatn A, Ishii T, Elazar Z, Komatsu M, Dikic I, Johansen T: A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009, 33: 505-516. 10.1016/j.molcel.2009.01.020.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19250911" aria-label="PubMed reference 95">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXltFSnu7k%3D" aria-label="CAS reference 95">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 95" href="http://scholar.google.com/scholar_lookup?&title=A%20role%20for%20NBR1%20in%20autophagosomal%20degradation%20of%20ubiquitinated%20substrates&journal=Mol%20Cell&doi=10.1016%2Fj.molcel.2009.01.020&volume=33&pages=505-516&publication_year=2009&author=Kirkin%2CV&author=Lamark%2CT&author=Sou%2CYS&author=Bj%C3%B8rk%C3%B8y%2CG&author=Nunn%2CJL&author=Bruun%2CJA&author=Shvets%2CE&author=McEwan%2CDG&author=Clausen%2CTH&author=Wild%2CP&author=Bilusic%2CI&author=Theurillat%2CJP&author=%C3%98vervatn%2CA&author=Ishii%2CT&author=Elazar%2CZ&author=Komatsu%2CM&author=Dikic%2CI&author=Johansen%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="96."><p class="c-article-references__text" id="ref-CR96">Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Löhr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dötsch V, Ney PA, Dikic I: Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010, 11: 45-51. 10.1038/embor.2009.256.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20010802" aria-label="PubMed reference 96">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXhsFChtbbP" aria-label="CAS reference 96">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816619" aria-label="PubMed Central reference 96">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 96" href="http://scholar.google.com/scholar_lookup?&title=Nix%20is%20a%20selective%20autophagy%20receptor%20for%20mitochondrial%20clearance&journal=EMBO%20Rep&doi=10.1038%2Fembor.2009.256&volume=11&pages=45-51&publication_year=2010&author=Novak%2CI&author=Kirkin%2CV&author=McEwan%2CDG&author=Zhang%2CJ&author=Wild%2CP&author=Rozenknop%2CA&author=Rogov%2CV&author=L%C3%B6hr%2CF&author=Popovic%2CD&author=Occhipinti%2CA&author=Reichert%2CAS&author=Terzic%2CJ&author=D%C3%B6tsch%2CV&author=Ney%2CPA&author=Dikic%2CI"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="97."><p class="c-article-references__text" id="ref-CR97">Schwarten M, Mohrluder J, Ma P, Stoldt M, Thielmann Y, Stangler T, Hersch N, Hoffmann B, Merkel R, Willbold D: Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy. 2009, 5: 690-698. 10.4161/auto.5.5.8494.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19363302" aria-label="PubMed reference 97">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXpvFCisr4%3D" aria-label="CAS reference 97">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 97" href="http://scholar.google.com/scholar_lookup?&title=Nix%20directly%20binds%20to%20GABARAP%3A%20a%20possible%20crosstalk%20between%20apoptosis%20and%20autophagy&journal=Autophagy&doi=10.4161%2Fauto.5.5.8494&volume=5&pages=690-698&publication_year=2009&author=Schwarten%2CM&author=Mohrluder%2CJ&author=Ma%2CP&author=Stoldt%2CM&author=Thielmann%2CY&author=Stangler%2CT&author=Hersch%2CN&author=Hoffmann%2CB&author=Merkel%2CR&author=Willbold%2CD"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="98."><p class="c-article-references__text" id="ref-CR98">Filimonenko M, Stuffers S, Raiborg C, Yamamoto A, Malerod L, Fisher EM, Isaacs A, Brech A, Stenmark H, Simonsen A: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol. 2007, 179: 485-500. 10.1083/jcb.200702115.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17984323" aria-label="PubMed reference 98">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXht12jsbzO" aria-label="CAS reference 98">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064794" aria-label="PubMed Central reference 98">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 98" href="http://scholar.google.com/scholar_lookup?&title=Functional%20multivesicular%20bodies%20are%20required%20for%20autophagic%20clearance%20of%20protein%20aggregates%20associated%20with%20neurodegenerative%20disease&journal=J%20Cell%20Biol&doi=10.1083%2Fjcb.200702115&volume=179&pages=485-500&publication_year=2007&author=Filimonenko%2CM&author=Stuffers%2CS&author=Raiborg%2CC&author=Yamamoto%2CA&author=Malerod%2CL&author=Fisher%2CEM&author=Isaacs%2CA&author=Brech%2CA&author=Stenmark%2CH&author=Simonsen%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="99."><p class="c-article-references__text" id="ref-CR99">Clausen TH, Lamark T, Isakson P, Finley K, Larsen KB, Brech A, Øvervatn A, Stenmark H, Bjørkøy G, Simonsen A, Johansen T: p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy. 2010, 6: 330-344. 10.4161/auto.6.3.11226.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20168092" aria-label="PubMed reference 99">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXpt1WjtLo%3D" aria-label="CAS reference 99">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 99" href="http://scholar.google.com/scholar_lookup?&title=p62%2FSQSTM1%20and%20ALFY%20interact%20to%20facilitate%20the%20formation%20of%20p62%20bodies%2FALIS%20and%20their%20degradation%20by%20autophagy&journal=Autophagy&doi=10.4161%2Fauto.6.3.11226&volume=6&pages=330-344&publication_year=2010&author=Clausen%2CTH&author=Lamark%2CT&author=Isakson%2CP&author=Finley%2CK&author=Larsen%2CKB&author=Brech%2CA&author=%C3%98vervatn%2CA&author=Stenmark%2CH&author=Bj%C3%B8rk%C3%B8y%2CG&author=Simonsen%2CA&author=Johansen%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="100."><p class="c-article-references__text" id="ref-CR100">Filimonenko M, Isakson P, Finley KD, Anderson M, Jeong H, Melia TJ, Bartlett BJ, Myers KM, Birkeland HC, Lamark T, Krainc D, Brech A, Stenmark H, Simonsen A, Yamamoto A: The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell. 2010, 38: 265-279. 10.1016/j.molcel.2010.04.007.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20417604" aria-label="PubMed reference 100">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXms1alsrY%3D" aria-label="CAS reference 100">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867245" aria-label="PubMed Central reference 100">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 100" href="http://scholar.google.com/scholar_lookup?&title=The%20selective%20macroautophagic%20degradation%20of%20aggregated%20proteins%20requires%20the%20PI3P-binding%20protein%20Alfy&journal=Mol%20Cell&doi=10.1016%2Fj.molcel.2010.04.007&volume=38&pages=265-279&publication_year=2010&author=Filimonenko%2CM&author=Isakson%2CP&author=Finley%2CKD&author=Anderson%2CM&author=Jeong%2CH&author=Melia%2CTJ&author=Bartlett%2CBJ&author=Myers%2CKM&author=Birkeland%2CHC&author=Lamark%2CT&author=Krainc%2CD&author=Brech%2CA&author=Stenmark%2CH&author=Simonsen%2CA&author=Yamamoto%2CA"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="101."><p class="c-article-references__text" id="ref-CR101">Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F: The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol. 2009, 10: 1215-1221. 10.1038/ni.1800.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19820708" aria-label="PubMed reference 101">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXht1Cmu7%2FL" aria-label="CAS reference 101">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 101" href="http://scholar.google.com/scholar_lookup?&title=The%20TBK1%20adaptor%20and%20autophagy%20receptor%20NDP52%20restricts%20the%20proliferation%20of%20ubiquitin-coated%20bacteria&journal=Nat%20Immunol&doi=10.1038%2Fni.1800&volume=10&pages=1215-1221&publication_year=2009&author=Thurston%2CTL&author=Ryzhakov%2CG&author=Bloor%2CS&author=von%20Muhlinen%2CN&author=Randow%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="102."><p class="c-article-references__text" id="ref-CR102">Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, Dötsch V, Bumann D, Dikic I: Phosphorylation of the autophagy receptor optineurin restricts <i>Salmonella</i> growth. Science. 2011, 333: 228-233. 10.1126/science.1205405.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21617041" aria-label="PubMed reference 102">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3MXotlGmtLo%3D" aria-label="CAS reference 102">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714538" aria-label="PubMed Central reference 102">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 102" href="http://scholar.google.com/scholar_lookup?&title=Phosphorylation%20of%20the%20autophagy%20receptor%20optineurin%20restricts%20Salmonella%20growth&journal=Science&doi=10.1126%2Fscience.1205405&volume=333&pages=228-233&publication_year=2011&author=Wild%2CP&author=Farhan%2CH&author=McEwan%2CDG&author=Wagner%2CS&author=Rogov%2CVV&author=Brady%2CNR&author=Richter%2CB&author=Korac%2CJ&author=Waidmann%2CO&author=Choudhary%2CC&author=D%C3%B6tsch%2CV&author=Bumann%2CD&author=Dikic%2CI"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="103."><p class="c-article-references__text" id="ref-CR103">Shvets E, Fass E, Scherz-Shouval R, Elazar Z: The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes. J Cell Sci. 2008, 121: 2685-2695. 10.1242/jcs.026005.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18653543" aria-label="PubMed reference 103">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXhtFKhu7rJ" aria-label="CAS reference 103">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 103" href="http://scholar.google.com/scholar_lookup?&title=The%20N-terminus%20and%20Phe52%20residue%20of%20LC3%20recruit%20p62%2FSQSTM1%20into%20autophagosomes&journal=J%20Cell%20Sci&doi=10.1242%2Fjcs.026005&volume=121&pages=2685-2695&publication_year=2008&author=Shvets%2CE&author=Fass%2CE&author=Scherz-Shouval%2CR&author=Elazar%2CZ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="104."><p class="c-article-references__text" id="ref-CR104">Ichimura Y, Kumanomidou T, Sou YS, Mizushima T, Ezaki J, Ueno T, Kominami E, Yamane T, Tanaka K, Komatsu M: Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem. 2008, 283: 22847-22857. 10.1074/jbc.M802182200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18524774" aria-label="PubMed reference 104">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXpsVKmt7o%3D" aria-label="CAS reference 104">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 104" href="http://scholar.google.com/scholar_lookup?&title=Structural%20basis%20for%20sorting%20mechanism%20of%20p62%20in%20selective%20autophagy&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M802182200&volume=283&pages=22847-22857&publication_year=2008&author=Ichimura%2CY&author=Kumanomidou%2CT&author=Sou%2CYS&author=Mizushima%2CT&author=Ezaki%2CJ&author=Ueno%2CT&author=Kominami%2CE&author=Yamane%2CT&author=Tanaka%2CK&author=Komatsu%2CM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="105."><p class="c-article-references__text" id="ref-CR105">Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007, 282: 24131-24145. 10.1074/jbc.M702824200.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17580304" aria-label="PubMed reference 105">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXoslOntb0%3D" aria-label="CAS reference 105">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 105" href="http://scholar.google.com/scholar_lookup?&title=p62%2FSQSTM1%20binds%20directly%20to%20Atg8%2FLC3%20to%20facilitate%20degradation%20of%20ubiquitinated%20protein%20aggregates%20by%20autophagy&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M702824200&volume=282&pages=24131-24145&publication_year=2007&author=Pankiv%2CS&author=Clausen%2CTH&author=Lamark%2CT&author=Brech%2CA&author=Bruun%2CJA&author=Outzen%2CH&author=Overvatn%2CA&author=Bjorkoy%2CG&author=Johansen%2CT"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="106."><p class="c-article-references__text" id="ref-CR106">Kraft C, Peter M, Hofmann K: Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol. 2010, 12: 836-841. 10.1038/ncb0910-836.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20811356" aria-label="PubMed reference 106">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtFSju7zI" aria-label="CAS reference 106">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 106" href="http://scholar.google.com/scholar_lookup?&title=Selective%20autophagy%3A%20ubiquitin-mediated%20recognition%20and%20beyond&journal=Nat%20Cell%20Biol&doi=10.1038%2Fncb0910-836&volume=12&pages=836-841&publication_year=2010&author=Kraft%2CC&author=Peter%2CM&author=Hofmann%2CK"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="107."><p class="c-article-references__text" id="ref-CR107">Yamaguchi M, Noda NN, Nakatogawa H, Kumeta H, Ohsumi Y, Inagaki F: Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3-Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway. J Biol Chem. 2010, 285: 29599-29607. 10.1074/jbc.M110.113670.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20615880" aria-label="PubMed reference 107">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtFCnsL7N" aria-label="CAS reference 107">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937991" aria-label="PubMed Central reference 107">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 107" href="http://scholar.google.com/scholar_lookup?&title=Autophagy-related%20protein%208%20%28Atg8%29%20family%20interacting%20motif%20in%20Atg3%20mediates%20the%20Atg3-Atg8%20interaction%20and%20is%20crucial%20for%20the%20cytoplasm-to-vacuole%20targeting%20pathway&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M110.113670&volume=285&pages=29599-29607&publication_year=2010&author=Yamaguchi%2CM&author=Noda%2CNN&author=Nakatogawa%2CH&author=Kumeta%2CH&author=Ohsumi%2CY&author=Inagaki%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="108."><p class="c-article-references__text" id="ref-CR108">Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, Fujioka Y, Ohsumi Y, Inagaki F: Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008, 13: 1211-1218. 10.1111/j.1365-2443.2008.01238.x.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19021777" aria-label="PubMed reference 108">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1MXnslem" aria-label="CAS reference 108">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 108" href="http://scholar.google.com/scholar_lookup?&title=Structural%20basis%20of%20target%20recognition%20by%20Atg8%2FLC3%20during%20selective%20autophagy&journal=Genes%20Cells&doi=10.1111%2Fj.1365-2443.2008.01238.x&volume=13&pages=1211-1218&publication_year=2008&author=Noda%2CNN&author=Kumeta%2CH&author=Nakatogawa%2CH&author=Satoo%2CK&author=Adachi%2CW&author=Ishii%2CJ&author=Fujioka%2CY&author=Ohsumi%2CY&author=Inagaki%2CF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="109."><p class="c-article-references__text" id="ref-CR109">Jiang S, Heller B, Tagliabracci VS, Zhai L, Irimia JM, DePaoli-Roach AA, Wells CD, Skurat AV, Roach PJ: Starch binding domain-containing protein 1/genethonin 1 is a novel participant in glycogen metabolism. J Biol Chem. 2010, 285: 34960-34971. 10.1074/jbc.M110.150839.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20810658" aria-label="PubMed reference 109">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtlGktbjJ" aria-label="CAS reference 109">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966110" aria-label="PubMed Central reference 109">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 109" href="http://scholar.google.com/scholar_lookup?&title=Starch%20binding%20domain-containing%20protein%201%2Fgenethonin%201%20is%20a%20novel%20participant%20in%20glycogen%20metabolism&journal=J%20Biol%20Chem&doi=10.1074%2Fjbc.M110.150839&volume=285&pages=34960-34971&publication_year=2010&author=Jiang%2CS&author=Heller%2CB&author=Tagliabracci%2CVS&author=Zhai%2CL&author=Irimia%2CJM&author=DePaoli-Roach%2CAA&author=Wells%2CCD&author=Skurat%2CAV&author=Roach%2CPJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="110."><p class="c-article-references__text" id="ref-CR110">Kuma A, Matsui M, Mizushima N: LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization. Autophagy. 2007, 3: 323-328.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17387262" aria-label="PubMed reference 110">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD2sXhtVGrtLbO" aria-label="CAS reference 110">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 110" href="http://scholar.google.com/scholar_lookup?&title=LC3%2C%20an%20autophagosome%20marker%2C%20can%20be%20incorporated%20into%20protein%20aggregates%20independent%20of%20autophagy%3A%20caution%20in%20the%20interpretation%20of%20LC3%20localization&journal=Autophagy&volume=3&pages=323-328&publication_year=2007&author=Kuma%2CA&author=Matsui%2CM&author=Mizushima%2CN"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="111."><p class="c-article-references__text" id="ref-CR111">Ruiz-Trillo I, Roger AJ, Burger G, Gray MW, Lang BF: A phylogenomic investigation into the origin of metazoa. Mol Biol Evol. 2008, 25: 664-672. 10.1093/molbev/msn006.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=18184723" aria-label="PubMed reference 111">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BD1cXksFWktr8%3D" aria-label="CAS reference 111">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 111" href="http://scholar.google.com/scholar_lookup?&title=A%20phylogenomic%20investigation%20into%20the%20origin%20of%20metazoa&journal=Mol%20Biol%20Evol&doi=10.1093%2Fmolbev%2Fmsn006&volume=25&pages=664-672&publication_year=2008&author=Ruiz-Trillo%2CI&author=Roger%2CAJ&author=Burger%2CG&author=Gray%2CMW&author=Lang%2CBF"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="112."><p class="c-article-references__text" id="ref-CR112">Salzberg Y, Eldar T, Karminsky OD, Itach SB, Pietrokovski S, Don J: Meig1 deficiency causes a severe defect in mouse spermatogenesis. Dev Biol. 2010, 338: 158-167. 10.1016/j.ydbio.2009.11.028.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=20004656" aria-label="PubMed reference 112">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXhtlGgurg%3D" aria-label="CAS reference 112">CAS</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 112" href="http://scholar.google.com/scholar_lookup?&title=Meig1%20deficiency%20causes%20a%20severe%20defect%20in%20mouse%20spermatogenesis&journal=Dev%20Biol&doi=10.1016%2Fj.ydbio.2009.11.028&volume=338&pages=158-167&publication_year=2010&author=Salzberg%2CY&author=Eldar%2CT&author=Karminsky%2COD&author=Itach%2CSB&author=Pietrokovski%2CS&author=Don%2CJ"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="113."><p class="c-article-references__text" id="ref-CR113">Schneider TD, Stephens RM: Sequence logos: a new way to display consensus sequences. Nucleic Acids Res. 1990, 18: 6097-6100. 10.1093/nar/18.20.6097.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=2172928" aria-label="PubMed reference 113">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DyaK3MXitVGmuw%3D%3D" aria-label="CAS reference 113">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC332411" aria-label="PubMed Central reference 113">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 113" href="http://scholar.google.com/scholar_lookup?&title=Sequence%20logos%3A%20a%20new%20way%20to%20display%20consensus%20sequences&journal=Nucleic%20Acids%20Res&doi=10.1093%2Fnar%2F18.20.6097&volume=18&pages=6097-6100&publication_year=1990&author=Schneider%2CTD&author=Stephens%2CRM"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="114."><p class="c-article-references__text" id="ref-CR114">Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH: CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 2011, 39: D225-D229. 10.1093/nar/gkq1189.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21109532" aria-label="PubMed reference 114">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3sXivF2ltb8%3D" aria-label="CAS reference 114">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013737" aria-label="PubMed Central reference 114">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 114" href="http://scholar.google.com/scholar_lookup?&title=CDD%3A%20a%20Conserved%20Domain%20Database%20for%20the%20functional%20annotation%20of%20proteins&journal=Nucleic%20Acids%20Res&doi=10.1093%2Fnar%2Fgkq1189&volume=39&pages=D225-D229&publication_year=2011&author=Marchler-Bauer%2CA&author=Lu%2CS&author=Anderson%2CJB&author=Chitsaz%2CF&author=Derbyshire%2CMK&author=DeWeese-Scott%2CC&author=Fong%2CJH&author=Geer%2CLY&author=Geer%2CRC&author=Gonzales%2CNR&author=Gwadz%2CM&author=Hurwitz%2CDI&author=Jackson%2CJD&author=Ke%2CZ&author=Lanczycki%2CCJ&author=Lu%2CF&author=Marchler%2CGH&author=Mullokandov%2CM&author=Omelchenko%2CMV&author=Robertson%2CCL&author=Song%2CJS&author=Thanki%2CN&author=Yamashita%2CRA&author=Zhang%2CD&author=Zhang%2CN&author=Zheng%2CC&author=Bryant%2CSH"> Google Scholar</a> </p></li><li class="c-article-references__item js-c-reading-companion-references-item" data-counter="115."><p class="c-article-references__text" id="ref-CR115">Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A: The Pfam protein families database. Nucleic Acids Res. 2010, 38: D211-D222. 10.1093/nar/gkp985.</p><p class="c-article-references__links u-hide-print"><a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed reference" data-track-action="pubmed reference" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19920124" aria-label="PubMed reference 115">PubMed</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="cas reference" data-track-action="cas reference" href="/articles/cas-redirect/1:CAS:528:DC%2BC3cXktlyhsA%3D%3D" aria-label="CAS reference 115">CAS</a> <a data-track="click_references" rel="nofollow noopener" data-track-label="link" data-track-item_id="link" data-track-value="pubmed central reference" data-track-action="pubmed central reference" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808889" aria-label="PubMed Central reference 115">PubMed Central</a> <a data-track="click_references" data-track-action="google scholar reference" data-track-value="google scholar reference" data-track-label="link" data-track-item_id="link" rel="nofollow noopener" aria-label="Google Scholar reference 115" href="http://scholar.google.com/scholar_lookup?&title=The%20Pfam%20protein%20families%20database&journal=Nucleic%20Acids%20Res&doi=10.1093%2Fnar%2Fgkp985&volume=38&pages=D211-D222&publication_year=2010&author=Finn%2CRD&author=Mistry%2CJ&author=Tate%2CJ&author=Coggill%2CP&author=Heger%2CA&author=Pollington%2CJE&author=Gavin%2COL&author=Gunasekaran%2CP&author=Ceric%2CG&author=Forslund%2CK&author=Holm%2CL&author=Sonnhammer%2CEL&author=Eddy%2CSR&author=Bateman%2CA"> Google Scholar</a> </p></li></ol><p class="c-article-references__download u-hide-print"><a data-track="click" data-track-action="download citation references" data-track-label="link" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1186/gb-2011-12-7-226?format=refman&flavour=references">Download references<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p></div></div></div></section></div><section data-title="Acknowledgements"><div class="c-article-section" id="Ack1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Ack1">Acknowledgements</h2><div class="c-article-section__content" id="Ack1-content"><p>ZE is the incumbent of the Harold Korda Chair of Biology and is supported in part by the Legacy Heritage Fund, and by the Louis Brause Philanthropic Fund. SP holds a Hermann and Lilly Schilling Foundation chair.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Department of Biological Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</p><p class="c-article-author-affiliation__authors-list">Tomer Shpilka, Hilla Weidberg & Zvulun Elazar</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Department of Molecular Genetics, The Weizmann Institute of Science, 76100, Rehovot, Israel</p><p class="c-article-author-affiliation__authors-list">Shmuel Pietrokovski</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Tomer-Shpilka-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Tomer Shpilka</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="https://www.biomedcentral.com/search?query=author%23Tomer%20Shpilka" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Tomer%20Shpilka" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Tomer%20Shpilka%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Hilla-Weidberg-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Hilla Weidberg</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="https://www.biomedcentral.com/search?query=author%23Hilla%20Weidberg" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Hilla%20Weidberg" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Hilla%20Weidberg%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Shmuel-Pietrokovski-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">Shmuel Pietrokovski</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="https://www.biomedcentral.com/search?query=author%23Shmuel%20Pietrokovski" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Shmuel%20Pietrokovski" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Shmuel%20Pietrokovski%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Zvulun-Elazar-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Zvulun Elazar</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="https://www.biomedcentral.com/search?query=author%23Zvulun%20Elazar" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Zvulun%20Elazar" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Zvulun%20Elazar%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li></ol></div><h3 class="c-article__sub-heading" id="corresponding-author">Corresponding authors</h3><p id="corresponding-author-list">Correspondence to <a id="corresp-c1" href="mailto:shmuel.pietrokovski@weizmann.ac.il">Shmuel Pietrokovski</a> or <a id="corresp-c2" href="mailto:zvulun.elazar@weizmann.ac.il">Zvulun Elazar</a>.</p></div></div></section><section data-title="Authors’ original submitted files for images"><div class="c-article-section" id="Sec9-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec9">Authors’ original submitted files for images</h2><div class="c-article-section__content" id="Sec9-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><p>Below are the links to the authors’ original submitted files for images.</p><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM1"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="authors’ original file for figure 1" href="https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_2554_MOESM1_ESM.pdf" data-supp-info-image="">Authors’ original file for figure 1</a></h3></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM2"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="authors’ original file for figure 2" href="https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_2554_MOESM2_ESM.pdf" data-supp-info-image="">Authors’ original file for figure 2</a></h3></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM3"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="authors’ original file for figure 3" href="https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_2554_MOESM3_ESM.pdf" data-supp-info-image="">Authors’ original file for figure 3</a></h3></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM4"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="authors’ original file for figure 4" href="https://static-content.springer.com/esm/art%3A10.1186%2Fgb-2011-12-7-226/MediaObjects/13059_2011_2554_MOESM4_ESM.pdf" data-supp-info-image="">Authors’ original file for figure 4</a></h3></div></div></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"><p class="c-article-rights"><a data-track="click" data-track-action="view rights and permissions" data-track-label="link" href="https://s100.copyright.com/AppDispatchServlet?title=Atg8%3A%20an%20autophagy-related%20ubiquitin-like%20protein%20family&author=Tomer%20Shpilka%20et%20al&contentID=10.1186%2Fgb-2011-12-7-226&copyright=BioMed%20Central%20Ltd&publication=1474-760X&publicationDate=2011-07-27&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions</a></p></div></div></section><section aria-labelledby="article-info" data-title="About this article"><div class="c-article-section" id="article-info-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="article-info">About this article</h2><div class="c-article-section__content" id="article-info-content"><div class="c-bibliographic-information"><div class="c-bibliographic-information__column"><h3 class="c-article__sub-heading" id="citeas">Cite this article</h3><p class="c-bibliographic-information__citation">Shpilka, T., Weidberg, H., Pietrokovski, S. <i>et al.</i> Atg8: an autophagy-related ubiquitin-like protein family. <i>Genome Biol</i> <b>12</b>, 226 (2011). https://doi.org/10.1186/gb-2011-12-7-226</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1186/gb-2011-12-7-226?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-07-27">27 July 2011</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1186/gb-2011-12-7-226</span></p></li></ul><div data-component="share-box"><div class="c-article-share-box u-display-none" hidden=""><h3 class="c-article__sub-heading">Share this article</h3><p class="c-article-share-box__description">Anyone you share the following link with will be able to read this content:</p><button class="js-get-share-url c-article-share-box__button" type="button" id="get-share-url" data-track="click" data-track-label="button" data-track-external="" data-track-action="get shareable link">Get shareable link</button><div class="js-no-share-url-container u-display-none" hidden=""><p class="js-c-article-share-box__no-sharelink-info c-article-share-box__no-sharelink-info">Sorry, a shareable link is not currently available for this article.</p></div><div class="js-share-url-container u-display-none" hidden=""><p class="js-share-url c-article-share-box__only-read-input" id="share-url" data-track="click" data-track-label="button" data-track-action="select share url"></p><button class="js-copy-share-url c-article-share-box__button--link-like" type="button" id="copy-share-url" data-track="click" data-track-label="button" data-track-action="copy share url" data-track-external="">Copy to clipboard</button></div><p class="js-c-article-share-box__additional-info c-article-share-box__additional-info"> Provided by the Springer Nature SharedIt content-sharing initiative </p></div></div><h3 class="c-article__sub-heading">Keywords</h3><ul class="c-article-subject-list"><li class="c-article-subject-list__subject"><span><a href="/search?query=Autophagosome%20Formation&facet-discipline="Life%20Sciences"" data-track="click" data-track-action="view keyword" data-track-label="link">Autophagosome Formation</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Autophagic%20Process&facet-discipline="Life%20Sciences"" data-track="click" data-track-action="view keyword" data-track-label="link">Autophagic Process</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Atg8%20Gene&facet-discipline="Life%20Sciences"" data-track="click" data-track-action="view keyword" data-track-label="link">Atg8 Gene</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Multicellular%20Animal&facet-discipline="Life%20Sciences"" data-track="click" data-track-action="view keyword" data-track-label="link">Multicellular Animal</a></span></li><li class="c-article-subject-list__subject"><span><a href="/search?query=Atg8%20Protein&facet-discipline="Life%20Sciences"" data-track="click" data-track-action="view keyword" data-track-label="link">Atg8 Protein</a></span></li></ul><div data-component="article-info-list"></div></div></div></div></div></section> </article> </main> <div class="c-article-extras u-text-sm u-hide-print" data-container-type="reading-companion" data-track-component="reading companion"> <aside> <div data-test="download-article-link-wrapper" class="js-context-bar-sticky-point-desktop" data-track-context="reading companion"> <div class="c-pdf-download u-clear-both"> <a href="//genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2011-12-7-226.pdf" class="u-button u-button--full-width u-button--primary u-justify-content-space-between c-pdf-download__link" data-article-pdf="true" data-readcube-pdf-url="true" data-test="pdf-link" data-draft-ignore="true" data-track="content_download" data-track-type="article pdf download" data-track-action="download pdf" data-track-label="link" data-track-external download> <span class="c-pdf-download__text">Download PDF</span> <svg aria-hidden="true" focusable="false" width="16" height="16" class="u-icon"><use xlink:href="#icon-download"/></svg> </a> </div> </div> <div class="c-reading-companion"> <div class="c-reading-companion__sticky" data-component="reading-companion-sticky" data-test="reading-companion-sticky"> <div class="c-reading-companion__panel c-reading-companion__sections c-reading-companion__panel--active" id="tabpanel-sections"> <div class="js-ad u-lazy-ad-wrapper u-mt-16 u-hide" data-component-mpu> <aside class="adsbox c-ad c-ad--300x250 u-mt-16" data-component-mpu> <div class="c-ad__inner"> <p class="c-ad__label">Advertisement</p> <div id="div-gpt-ad-MPU1" data-ad-type="MPU1" data-test="MPU1-ad" data-pa11y-ignore data-gpt data-gpt-unitpath="/270604982/bmc/genomebiology/articles" data-gpt-sizes="300x250" data-gpt-targeting="pos=MPU1;doi=10.1186/gb-2011-12-7-226;type=article;kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein;pmc=L32030,B12008,L32020,L32010,L15001,L21001;" > <noscript> <a href="//pubads.g.doubleclick.net/gampad/jump?iu=/270604982/bmc/genomebiology/articles&sz=300x250&pos=MPU1&doi=10.1186/gb-2011-12-7-226&type=article&kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein&pmc=L32030,B12008,L32020,L32010,L15001,L21001&"> <img data-test="gpt-advert-fallback-img" src="//pubads.g.doubleclick.net/gampad/ad?iu=/270604982/bmc/genomebiology/articles&sz=300x250&pos=MPU1&doi=10.1186/gb-2011-12-7-226&type=article&kwrd=Autophagosome Formation,Autophagic Process,Atg8 Gene,Multicellular Animal,Atg8 Protein&pmc=L32030,B12008,L32020,L32010,L15001,L21001&" alt="Advertisement" width="300" height="250"> </a> </noscript> </div> </div> </aside> </div> </div> <div class="c-reading-companion__panel c-reading-companion__figures c-reading-companion__panel--full-width" id="tabpanel-figures"></div> <div class="c-reading-companion__panel c-reading-companion__references c-reading-companion__panel--full-width" id="tabpanel-references"></div> </div> </div> </aside> </div> </div> <div class="c-journal-footer"> <div class="c-journal-footer__inner"> <div class="c-journal-footer__summary"> <h4 class="c-journal-title c-journal-title--footer"> <span class="c-journal-title__text">Genome Biology</span> </h4> <p class="c-journal-footer__issn">ISSN: 1474-760X</p> </div> <div class="c-journal-footer__contact"> <h4 class="c-journal-footer__contact-title ">Contact us</h4> <ul class="c-journal-footer__contact-list"> <li class="c-journal-footer__contact-item">General enquiries: <a href="mailto:journalsubmissions@springernature.com">journalsubmissions@springernature.com</a></li> </ul> </div> </div> </div> <img rel="nofollow" class='tracker' style='display:none' src='/track/article/10.1186/gb-2011-12-7-226' alt=""/> <footer> <div class="c-publisher-footer u-color-inherit" data-test="publisher-footer"> <div class="u-container"> <div class="u-display-flex u-flex-wrap u-justify-content-space-between" data-test="publisher-footer-menu"> <div class="u-display-flex"> <ul class="c-list-group c-list-group--sm u-mr-24 u-mb-16"> <li class="c-list-group__item"> <a class="u-gray-link" href="https://blogs.biomedcentral.com/">Read more on our blogs</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/login">Receive BMC newsletters</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/account">Manage article alerts</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="https://authorservices.springernature.com/go/sn/?utm_source=Website&utm_medium=BMC&utm_campaign=SNAS+Referrals+2022&utm_id=ref2022">Language editing for authors</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="https://authorservices.springernature.com/go/sn/?utm_source=Website&utm_medium=BMC&utm_campaign=SNAS+Referrals+2022&utm_id=ref2022">Scientific editing for authors</a> </li> </ul> <ul class="c-list-group c-list-group--sm u-mr-24 u-mb-16"> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/about/policies">Policies</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/accessibility">Accessibility</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/about/press-centre">Press center</a> </li> </ul> <ul class="c-list-group c-list-group--sm u-mr-24 u-mb-16"> <li class="c-list-group__item"> <a class="u-gray-link" href="https://support.biomedcentral.com/support/home">Support and Contact</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="https://biomedcentral.typeform.com/to/VLXboo">Leave feedback</a> </li> <li class="c-list-group__item"> <a class="u-gray-link" href="//www.biomedcentral.com/about/jobs">Careers</a> </li> </ul> </div> <div class="u-mb-24"> <h3 id="social-menu" class="u-text-sm u-reset-margin u-text-normal">Follow BMC</h3> <ul class="u-display-flex u-list-reset" data-test="footer-social-links"> <li class="u-mt-8 u-mr-8"> <a href="https://twitter.com/biomedcentral" data-track="click" data-track-category="Social" data-track-action="Clicked BMC Twitter" class="u-gray-link"> <span class="u-visually-hidden">BMC Twitter page</span> <svg class="u-icon u-text-lg" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-twitter-bordered"></use> </svg> </a> </li> <li class="u-mt-8 u-mr-8"> <a href="https://www.facebook.com/BioMedCentral" data-track="click" data-track-category="Social" data-track-action="Clicked BMC Facebook" class="u-gray-link"> <span class="u-visually-hidden">BMC Facebook page</span> <svg class="u-icon u-text-lg" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-facebook-bordered"></use> </svg> </a> </li> <li class="u-mt-8 u-mr-8"> <a href="http://www.weibo.com/biomedcentral" data-track="click" data-track-category="Social" data-track-action="Clicked BMC Weibo" class="u-gray-link"> <span class="u-visually-hidden">BMC Weibo page</span> <svg class="u-icon u-text-lg" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-weibo-bordered"></use> </svg> </a> </li> </ul> </div> </div> <p class="u-reset-margin"> By using this website, you agree to our <a class="u-gray-link" href="//www.biomedcentral.com/terms-and-conditions">Terms and Conditions</a>, <a class="u-gray-link" href="https://www.springernature.com/ccpa">Your US state privacy rights</a>, <a class="u-gray-link" href="//www.biomedcentral.com/privacy-statement">Privacy statement</a> and <a class="u-gray-link" href="//www.biomedcentral.com/cookies" data-test="cookie-link">Cookies</a> policy. <a class="u-gray-link" data-cc-action="preferences" href="javascript:void(0);">Your privacy choices/Manage cookies</a> we use in the preference centre. </p> </div> </div> <div class="c-corporate-footer"> <div class="u-container"> <img src=/static/images/logo-springernature-acb40b85fb.svg class="c-corporate-footer__logo" alt="Springer Nature" itemprop="logo" role="img"> <p class="c-corporate-footer__legal" data-test="copyright"> © 2024 BioMed Central Ltd unless otherwise stated. Part of <a class="c-corporate-footer__link" href="https://www.springernature.com" itemscope itemtype="http://schema.org/Organization" itemid="#parentOrganization">Springer Nature</a>. </p> </div> </div> </footer> </div> <div class="u-visually-hidden" aria-hidden="true"> <?xml version="1.0" encoding="UTF-8"?><!DOCTYPE svg PUBLIC "-//W3C//DTD SVG 1.1//EN" "http://www.w3.org/Graphics/SVG/1.1/DTD/svg11.dtd"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><defs><path id="a" d="M0 .74h56.72v55.24H0z"/></defs><symbol id="icon-access" viewBox="0 0 18 18"><path d="m14 8c.5522847 0 1 .44771525 1 1v7h2.5c.2761424 0 .5.2238576.5.5v1.5h-18v-1.5c0-.2761424.22385763-.5.5-.5h2.5v-7c0-.55228475.44771525-1 1-1s1 .44771525 1 1v6.9996556h8v-6.9996556c0-.55228475.4477153-1 1-1zm-8 0 2 1v5l-2 1zm6 0v7l-2-1v-5zm-2.42653766-7.59857636 7.03554716 4.92488299c.4162533.29137735.5174853.86502537.226108 1.28127873-.1721584.24594054-.4534847.39241464-.7536934.39241464h-14.16284822c-.50810197 0-.92-.41189803-.92-.92 0-.30020869.1464741-.58153499.39241464-.75369337l7.03554714-4.92488299c.34432015-.2410241.80260453-.2410241 1.14692468 0zm-.57346234 2.03988748-3.65526982 2.55868888h7.31053962z" fill-rule="evenodd"/></symbol><symbol id="icon-account" viewBox="0 0 18 18"><path d="m10.2379028 16.9048051c1.3083556-.2032362 2.5118471-.7235183 3.5294683-1.4798399-.8731327-2.5141501-2.0638925-3.935978-3.7673711-4.3188248v-1.27684611c1.1651924-.41183641 2-1.52307546 2-2.82929429 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.30621883.83480763 2.41745788 2 2.82929429v1.27684611c-1.70347856.3828468-2.89423845 1.8046747-3.76737114 4.3188248 1.01762123.7563216 2.22111275 1.2766037 3.52946833 1.4798399.40563808.0629726.81921174.0951949 1.23790281.0951949s.83226473-.0322223 1.2379028-.0951949zm4.3421782-2.1721994c1.4927655-1.4532925 2.419919-3.484675 2.419919-5.7326057 0-4.418278-3.581722-8-8-8s-8 3.581722-8 8c0 2.2479307.92715352 4.2793132 2.41991895 5.7326057.75688473-2.0164459 1.83949951-3.6071894 3.48926591-4.3218837-1.14534283-.70360829-1.90918486-1.96796271-1.90918486-3.410722 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.44275929-.763842 2.70711371-1.9091849 3.410722 1.6497664.7146943 2.7323812 2.3054378 3.4892659 4.3218837zm-5.580081 3.2673943c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-alert" viewBox="0 0 18 18"><path d="m4 10h2.5c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-3.08578644l-1.12132034 1.1213203c-.18753638.1875364-.29289322.4418903-.29289322.7071068v.1715729h14v-.1715729c0-.2652165-.1053568-.5195704-.2928932-.7071068l-1.7071068-1.7071067v-3.4142136c0-2.76142375-2.2385763-5-5-5-2.76142375 0-5 2.23857625-5 5zm3 4c0 1.1045695.8954305 2 2 2s2-.8954305 2-2zm-5 0c-.55228475 0-1-.4477153-1-1v-.1715729c0-.530433.21071368-1.0391408.58578644-1.4142135l1.41421356-1.4142136v-3c0-3.3137085 2.6862915-6 6-6s6 2.6862915 6 6v3l1.4142136 1.4142136c.3750727.3750727.5857864.8837805.5857864 1.4142135v.1715729c0 .5522847-.4477153 1-1 1h-4c0 1.6568542-1.3431458 3-3 3-1.65685425 0-3-1.3431458-3-3z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-broad" viewBox="0 0 16 16"><path d="m6.10307866 2.97190702v7.69043288l2.44965196-2.44676915c.38776071-.38730439 1.0088052-.39493524 1.38498697-.01919617.38609051.38563612.38643641 1.01053024-.00013864 1.39665039l-4.12239817 4.11754683c-.38616704.3857126-1.01187344.3861062-1.39846576-.0000311l-4.12258206-4.11773056c-.38618426-.38572979-.39254614-1.00476697-.01636437-1.38050605.38609047-.38563611 1.01018509-.38751562 1.4012233.00306241l2.44985644 2.4469734v-8.67638639c0-.54139983.43698413-.98042709.98493125-.98159081l7.89910522-.0043627c.5451687 0 .9871152.44142642.9871152.98595351s-.4419465.98595351-.9871152.98595351z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 14 15)"/></symbol><symbol id="icon-arrow-down" viewBox="0 0 16 16"><path d="m3.28337502 11.5302405 4.03074001 4.176208c.37758093.3912076.98937525.3916069 1.367372-.0000316l4.03091977-4.1763942c.3775978-.3912252.3838182-1.0190815.0160006-1.4001736-.3775061-.39113013-.9877245-.39303641-1.3700683.003106l-2.39538585 2.4818345v-11.6147896l-.00649339-.11662112c-.055753-.49733869-.46370161-.88337888-.95867408-.88337888-.49497246 0-.90292107.38604019-.95867408.88337888l-.00649338.11662112v11.6147896l-2.39518594-2.4816273c-.37913917-.39282218-.98637524-.40056175-1.35419292-.0194697-.37750607.3911302-.37784433 1.0249269.00013556 1.4165479z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-left" viewBox="0 0 16 16"><path d="m4.46975946 3.28337502-4.17620792 4.03074001c-.39120768.37758093-.39160691.98937525.0000316 1.367372l4.1763942 4.03091977c.39122514.3775978 1.01908149.3838182 1.40017357.0160006.39113012-.3775061.3930364-.9877245-.00310603-1.3700683l-2.48183446-2.39538585h11.61478958l.1166211-.00649339c.4973387-.055753.8833789-.46370161.8833789-.95867408 0-.49497246-.3860402-.90292107-.8833789-.95867408l-.1166211-.00649338h-11.61478958l2.4816273-2.39518594c.39282216-.37913917.40056173-.98637524.01946965-1.35419292-.39113012-.37750607-1.02492687-.37784433-1.41654791.00013556z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-right" viewBox="0 0 16 16"><path d="m11.5302405 12.716625 4.176208-4.03074003c.3912076-.37758093.3916069-.98937525-.0000316-1.367372l-4.1763942-4.03091981c-.3912252-.37759778-1.0190815-.38381821-1.4001736-.01600053-.39113013.37750607-.39303641.98772445.003106 1.37006824l2.4818345 2.39538588h-11.6147896l-.11662112.00649339c-.49733869.055753-.88337888.46370161-.88337888.95867408 0 .49497246.38604019.90292107.88337888.95867408l.11662112.00649338h11.6147896l-2.4816273 2.39518592c-.39282218.3791392-.40056175.9863753-.0194697 1.3541929.3911302.3775061 1.0249269.3778444 1.4165479-.0001355z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-sub" viewBox="0 0 16 16"><path d="m7.89692134 4.97190702v7.69043288l-2.44965196-2.4467692c-.38776071-.38730434-1.0088052-.39493519-1.38498697-.0191961-.38609047.3856361-.38643643 1.0105302.00013864 1.3966504l4.12239817 4.1175468c.38616704.3857126 1.01187344.3861062 1.39846576-.0000311l4.12258202-4.1177306c.3861843-.3857298.3925462-1.0047669.0163644-1.380506-.3860905-.38563612-1.0101851-.38751563-1.4012233.0030624l-2.44985643 2.4469734v-8.67638639c0-.54139983-.43698413-.98042709-.98493125-.98159081l-7.89910525-.0043627c-.54516866 0-.98711517.44142642-.98711517.98595351s.44194651.98595351.98711517.98595351z" fill-rule="evenodd"/></symbol><symbol id="icon-arrow-up" viewBox="0 0 16 16"><path d="m12.716625 4.46975946-4.03074003-4.17620792c-.37758093-.39120768-.98937525-.39160691-1.367372.0000316l-4.03091981 4.1763942c-.37759778.39122514-.38381821 1.01908149-.01600053 1.40017357.37750607.39113012.98772445.3930364 1.37006824-.00310603l2.39538588-2.48183446v11.61478958l.00649339.1166211c.055753.4973387.46370161.8833789.95867408.8833789.49497246 0 .90292107-.3860402.95867408-.8833789l.00649338-.1166211v-11.61478958l2.39518592 2.4816273c.3791392.39282216.9863753.40056173 1.3541929.01946965.3775061-.39113012.3778444-1.02492687-.0001355-1.41654791z" fill-rule="evenodd"/></symbol><symbol id="icon-article" viewBox="0 0 18 18"><path d="m13 15v-12.9906311c0-.0073595-.0019884-.0093689.0014977-.0093689l-11.00158888.00087166v13.00506804c0 .5482678.44615281.9940603.99415146.9940603h10.27350412c-.1701701-.2941734-.2675644-.6357129-.2675644-1zm-12 .0059397v-13.00506804c0-.5562408.44704472-1.00087166.99850233-1.00087166h11.00299537c.5510129 0 .9985023.45190985.9985023 1.0093689v2.9906311h3v9.9914698c0 1.1065798-.8927712 2.0085302-1.9940603 2.0085302h-12.01187942c-1.09954652 0-1.99406028-.8927712-1.99406028-1.9940603zm13-9.0059397v9c0 .5522847.4477153 1 1 1s1-.4477153 1-1v-9zm-10-2h7v4h-7zm1 1v2h5v-2zm-1 4h7v1h-7zm0 2h7v1h-7zm0 2h7v1h-7z" fill-rule="evenodd"/></symbol><symbol id="icon-audio" viewBox="0 0 18 18"><path d="m13.0957477 13.5588459c-.195279.1937043-.5119137.193729-.7072234.0000551-.1953098-.193674-.1953346-.5077061-.0000556-.7014104 1.0251004-1.0168342 1.6108711-2.3905226 1.6108711-3.85745208 0-1.46604976-.5850634-2.83898246-1.6090736-3.85566829-.1951894-.19379323-.1950192-.50782531.0003802-.70141028.1953993-.19358497.512034-.19341614.7072234.00037709 1.2094886 1.20083761 1.901635 2.8250555 1.901635 4.55670148 0 1.73268608-.6929822 3.35779608-1.9037571 4.55880738zm2.1233994 2.1025159c-.195234.193749-.5118687.1938462-.7072235.0002171-.1953548-.1936292-.1954528-.5076613-.0002189-.7014104 1.5832215-1.5711805 2.4881302-3.6939808 2.4881302-5.96012998 0-2.26581266-.9046382-4.3883241-2.487443-5.95944795-.1952117-.19377107-.1950777-.50780316.0002993-.70141031s.5120117-.19347426.7072234.00029682c1.7683321 1.75528196 2.7800854 4.12911258 2.7800854 6.66056144 0 2.53182498-1.0120556 4.90597838-2.7808529 6.66132328zm-14.21898205-3.6854911c-.5523759 0-1.00016505-.4441085-1.00016505-.991944v-3.96777631c0-.54783558.44778915-.99194407 1.00016505-.99194407h2.0003301l5.41965617-3.8393633c.44948677-.31842296 1.07413994-.21516983 1.39520191.23062232.12116339.16823446.18629727.36981184.18629727.57655577v12.01603479c0 .5478356-.44778914.9919441-1.00016505.9919441-.20845738 0-.41170538-.0645985-.58133413-.184766l-5.41965617-3.8393633zm0-.991944h2.32084805l5.68047235 4.0241292v-12.01603479l-5.68047235 4.02412928h-2.32084805z" fill-rule="evenodd"/></symbol><symbol id="icon-block" viewBox="0 0 24 24"><path d="m0 0h24v24h-24z" fill-rule="evenodd"/></symbol><symbol id="icon-book" viewBox="0 0 18 18"><path d="m4 13v-11h1v11h11v-11h-13c-.55228475 0-1 .44771525-1 1v10.2675644c.29417337-.1701701.63571286-.2675644 1-.2675644zm12 1h-13c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1h13zm0 3h-13c-1.1045695 0-2-.8954305-2-2v-12c0-1.1045695.8954305-2 2-2h13c.5522847 0 1 .44771525 1 1v14c0 .5522847-.4477153 1-1 1zm-8.5-13h6c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-6c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1 2h4c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-4c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-broad" viewBox="0 0 24 24"><path d="m9.18274226 7.81v7.7999954l2.48162734-2.4816273c.3928221-.3928221 1.0219731-.4005617 1.4030652-.0194696.3911301.3911301.3914806 1.0249268-.0001404 1.4165479l-4.17620796 4.1762079c-.39120769.3912077-1.02508144.3916069-1.41671995-.0000316l-4.1763942-4.1763942c-.39122514-.3912251-.39767006-1.0190815-.01657798-1.4001736.39113012-.3911301 1.02337106-.3930364 1.41951349.0031061l2.48183446 2.4818344v-8.7999954c0-.54911294.4426881-.99439484.99778758-.99557515l8.00221246-.00442485c.5522847 0 1 .44771525 1 1s-.4477153 1-1 1z" fill-rule="evenodd" transform="matrix(-1 0 0 -1 20.182742 24.805206)"/></symbol><symbol id="icon-calendar" viewBox="0 0 18 18"><path d="m12.5 0c.2761424 0 .5.21505737.5.49047852v.50952148h2c1.1072288 0 2 .89451376 2 2v12c0 1.1072288-.8945138 2-2 2h-12c-1.1072288 0-2-.8945138-2-2v-12c0-1.1072288.89451376-2 2-2h1v1h-1c-.55393837 0-1 .44579254-1 1v3h14v-3c0-.55393837-.4457925-1-1-1h-2v1.50952148c0 .27088381-.2319336.49047852-.5.49047852-.2761424 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.2319336-.49047852.5-.49047852zm3.5 7h-14v8c0 .5539384.44579254 1 1 1h12c.5539384 0 1-.4457925 1-1zm-11 6v1h-1v-1zm3 0v1h-1v-1zm3 0v1h-1v-1zm-6-2v1h-1v-1zm3 0v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-3-2v1h-1v-1zm6 0v1h-1v-1zm-3 0v1h-1v-1zm-5.5-9c.27614237 0 .5.21505737.5.49047852v.50952148h5v1h-5v1.50952148c0 .27088381-.23193359.49047852-.5.49047852-.27614237 0-.5-.21505737-.5-.49047852v-3.01904296c0-.27088381.23193359-.49047852.5-.49047852z" fill-rule="evenodd"/></symbol><symbol id="icon-cart" viewBox="0 0 18 18"><path d="m5 14c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm10 0c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm-10 1c-.55228475 0-1 .4477153-1 1s.44771525 1 1 1 1-.4477153 1-1-.44771525-1-1-1zm10 0c-.5522847 0-1 .4477153-1 1s.4477153 1 1 1 1-.4477153 1-1-.4477153-1-1-1zm-12.82032249-15c.47691417 0 .88746157.33678127.98070211.80449199l.23823144 1.19501025 13.36277974.00045554c.5522847.00001882.9999659.44774934.9999659 1.00004222 0 .07084994-.0075361.14150708-.022474.2107727l-1.2908094 5.98534344c-.1007861.46742419-.5432548.80388386-1.0571651.80388386h-10.24805106c-.59173366 0-1.07142857.4477153-1.07142857 1 0 .5128358.41361449.9355072.94647737.9932723l.1249512.0067277h10.35933776c.2749512 0 .4979349.2228539.4979349.4978051 0 .2749417-.2227336.4978951-.4976753.4980063l-10.35959736.0041886c-1.18346732 0-2.14285714-.8954305-2.14285714-2 0-.6625717.34520317-1.24989198.87690425-1.61383592l-1.63768102-8.19004794c-.01312273-.06561364-.01950005-.131011-.0196107-.19547395l-1.71961253-.00064219c-.27614237 0-.5-.22385762-.5-.5 0-.27614237.22385763-.5.5-.5zm14.53193359 2.99950224h-13.11300004l1.20580469 6.02530174c.11024034-.0163252.22327998-.02480398.33844139-.02480398h10.27064786z"/></symbol><symbol id="icon-chevron-less" viewBox="0 0 10 10"><path d="m5.58578644 4-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 -1 -1 0 9 9)"/></symbol><symbol id="icon-chevron-more" viewBox="0 0 10 10"><path d="m5.58578644 6-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4.00000002c-.39052429.3905243-1.02368927.3905243-1.41421356 0s-.39052429-1.02368929 0-1.41421358z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 1)"/></symbol><symbol id="icon-chevron-right" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-circle-fill" viewBox="0 0 16 16"><path d="m8 14c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-circle" viewBox="0 0 16 16"><path d="m8 12c2.209139 0 4-1.790861 4-4s-1.790861-4-4-4-4 1.790861-4 4 1.790861 4 4 4zm0 2c-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6 6 2.6862915 6 6-2.6862915 6-6 6z" fill-rule="evenodd"/></symbol><symbol id="icon-citation" viewBox="0 0 18 18"><path d="m8.63593473 5.99995183c2.20913897 0 3.99999997 1.79084375 3.99999997 3.99996146 0 1.40730761-.7267788 2.64486871-1.8254829 3.35783281 1.6240224.6764218 2.8754442 2.0093871 3.4610603 3.6412466l-1.0763845.000006c-.5310008-1.2078237-1.5108121-2.1940153-2.7691712-2.7181346l-.79002167-.329052v-1.023992l.63016577-.4089232c.8482885-.5504661 1.3698342-1.4895187 1.3698342-2.51898361 0-1.65683828-1.3431457-2.99996146-2.99999997-2.99996146-1.65685425 0-3 1.34312318-3 2.99996146 0 1.02946491.52154569 1.96851751 1.36983419 2.51898361l.63016581.4089232v1.023992l-.79002171.329052c-1.25835905.5241193-2.23817037 1.5103109-2.76917113 2.7181346l-1.07638453-.000006c.58561612-1.6318595 1.8370379-2.9648248 3.46106024-3.6412466-1.09870405-.7129641-1.82548287-1.9505252-1.82548287-3.35783281 0-2.20911771 1.790861-3.99996146 4-3.99996146zm7.36897597-4.99995183c1.1018574 0 1.9950893.89353404 1.9950893 2.00274083v5.994422c0 1.10608317-.8926228 2.00274087-1.9950893 2.00274087l-3.0049107-.0009037v-1l3.0049107.00091329c.5490631 0 .9950893-.44783123.9950893-1.00275046v-5.994422c0-.55646537-.4450595-1.00275046-.9950893-1.00275046h-14.00982141c-.54906309 0-.99508929.44783123-.99508929 1.00275046v5.9971821c0 .66666024.33333333.99999036 1 .99999036l2-.00091329v1l-2 .0009037c-1 0-2-.99999041-2-1.99998077v-5.9971821c0-1.10608322.8926228-2.00274083 1.99508929-2.00274083zm-8.5049107 2.9999711c.27614237 0 .5.22385547.5.5 0 .2761349-.22385763.5-.5.5h-4c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm3 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-1c-.27614237 0-.5-.2238651-.5-.5 0-.27614453.22385763-.5.5-.5zm4 0c.2761424 0 .5.22385547.5.5 0 .2761349-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238651-.5-.5 0-.27614453.2238576-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-close" viewBox="0 0 16 16"><path d="m2.29679575 12.2772478c-.39658757.3965876-.39438847 1.0328109-.00062148 1.4265779.39651227.3965123 1.03246768.3934888 1.42657791-.0006214l4.27724782-4.27724787 4.2772478 4.27724787c.3965876.3965875 1.0328109.3943884 1.4265779.0006214.3965123-.3965122.3934888-1.0324677-.0006214-1.4265779l-4.27724787-4.2772478 4.27724787-4.27724782c.3965875-.39658757.3943884-1.03281091.0006214-1.42657791-.3965122-.39651226-1.0324677-.39348875-1.4265779.00062148l-4.2772478 4.27724782-4.27724782-4.27724782c-.39658757-.39658757-1.03281091-.39438847-1.42657791-.00062148-.39651226.39651227-.39348875 1.03246768.00062148 1.42657791l4.27724782 4.27724782z" fill-rule="evenodd"/></symbol><symbol id="icon-collections" viewBox="0 0 18 18"><path d="m15 4c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2h1c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227l-.1166211-.00672773h-1v-1zm-4-3c1.1045695 0 2 .8954305 2 2v9c0 1.1045695-.8954305 2-2 2h-8c-1.1045695 0-2-.8954305-2-2v-9c0-1.1045695.8954305-2 2-2zm0 1h-8c-.51283584 0-.93550716.38604019-.99327227.88337887l-.00672773.11662113v9c0 .5128358.38604019.9355072.88337887.9932723l.11662113.0067277h8c.5128358 0 .9355072-.3860402.9932723-.8833789l.0067277-.1166211v-9c0-.51283584-.3860402-.93550716-.8833789-.99327227zm-1.5 7c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm0-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-5c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-compare" viewBox="0 0 18 18"><path d="m12 3c3.3137085 0 6 2.6862915 6 6s-2.6862915 6-6 6c-1.0928452 0-2.11744941-.2921742-2.99996061-.8026704-.88181407.5102749-1.90678042.8026704-3.00003939.8026704-3.3137085 0-6-2.6862915-6-6s2.6862915-6 6-6c1.09325897 0 2.11822532.29239547 3.00096303.80325037.88158756-.51107621 1.90619177-.80325037 2.99903697-.80325037zm-6 1c-2.76142375 0-5 2.23857625-5 5 0 2.7614237 2.23857625 5 5 5 .74397391 0 1.44999672-.162488 2.08451611-.4539116-1.27652344-1.1000812-2.08451611-2.7287264-2.08451611-4.5460884s.80799267-3.44600721 2.08434391-4.5463015c-.63434719-.29121054-1.34037-.4536985-2.08434391-.4536985zm6 0c-.7439739 0-1.4499967.16248796-2.08451611.45391156 1.27652341 1.10008123 2.08451611 2.72872644 2.08451611 4.54608844s-.8079927 3.4460072-2.08434391 4.5463015c.63434721.2912105 1.34037001.4536985 2.08434391.4536985 2.7614237 0 5-2.2385763 5-5 0-2.76142375-2.2385763-5-5-5zm-1.4162763 7.0005324h-3.16744736c.15614659.3572676.35283837.6927622.58425872 1.0006671h1.99892988c.23142036-.3079049.42811216-.6433995.58425876-1.0006671zm.4162763-2.0005324h-4c0 .34288501.0345146.67770871.10025909 1.0011864h3.79948181c.0657445-.32347769.1002591-.65830139.1002591-1.0011864zm-.4158423-1.99953894h-3.16831543c-.13859957.31730812-.24521946.651783-.31578599.99935097h3.79988742c-.0705665-.34756797-.1771864-.68204285-.315786-.99935097zm-1.58295822-1.999926-.08316107.06199199c-.34550042.27081213-.65446126.58611297-.91825862.93727862h2.00044041c-.28418626-.37830727-.6207872-.71499149-.99902072-.99927061z" fill-rule="evenodd"/></symbol><symbol id="icon-download-file" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.5046024 4c.27614237 0 .5.21637201.5.49209595v6.14827645l1.7462789-1.77990922c.1933927-.1971171.5125222-.19455839.7001689-.0069117.1932998.19329992.1910058.50899492-.0027774.70277812l-2.59089271 2.5908927c-.19483374.1948337-.51177825.1937771-.70556873-.0000133l-2.59099079-2.5909908c-.19484111-.1948411-.19043735-.5151448-.00279066-.70279146.19329987-.19329987.50465175-.19237083.70018565.00692852l1.74638684 1.78001764v-6.14827695c0-.27177709.23193359-.49209595.5-.49209595z" fill-rule="evenodd"/></symbol><symbol id="icon-download" viewBox="0 0 16 16"><path d="m12.9975267 12.999368c.5467123 0 1.0024733.4478567 1.0024733 1.000316 0 .5563109-.4488226 1.000316-1.0024733 1.000316h-9.99505341c-.54671233 0-1.00247329-.4478567-1.00247329-1.000316 0-.5563109.44882258-1.000316 1.00247329-1.000316zm-4.9975267-11.999368c.55228475 0 1 .44497754 1 .99589209v6.80214418l2.4816273-2.48241149c.3928222-.39294628 1.0219732-.4006883 1.4030652-.01947579.3911302.39125371.3914806 1.02525073-.0001404 1.41699553l-4.17620792 4.17752758c-.39120769.3913313-1.02508144.3917306-1.41671995-.0000316l-4.17639421-4.17771394c-.39122513-.39134876-.39767006-1.01940351-.01657797-1.40061601.39113012-.39125372 1.02337105-.3931606 1.41951349.00310701l2.48183446 2.48261871v-6.80214418c0-.55001601.44386482-.99589209 1-.99589209z" fill-rule="evenodd"/></symbol><symbol id="icon-editors" viewBox="0 0 18 18"><path d="m8.72592184 2.54588137c-.48811714-.34391207-1.08343326-.54588137-1.72592184-.54588137-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400182l-.79002171.32905522c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274v.9009805h-1v-.9009805c0-2.5479714 1.54557359-4.79153984 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4 1.09079823 0 2.07961816.43662103 2.80122451 1.1446278-.37707584.09278571-.7373238.22835063-1.07530267.40125357zm-2.72592184 14.45411863h-1v-.9009805c0-2.5479714 1.54557359-4.7915398 3.82548288-5.7411543-1.09870406-.71297106-1.82548288-1.95054399-1.82548288-3.3578652 0-2.209139 1.790861-4 4-4s4 1.790861 4 4c0 1.40732121-.7267788 2.64489414-1.8254829 3.3578652 2.2799093.9496145 3.8254829 3.1931829 3.8254829 5.7411543v.9009805h-1v-.9009805c0-2.1155483-1.2760206-4.0125067-3.2099783-4.8180274l-.7900217-.3290552v-1.02400184l.6301658-.40892721c.8482885-.55047139 1.3698342-1.489533 1.3698342-2.51900785 0-1.65685425-1.3431458-3-3-3-1.65685425 0-3 1.34314575-3 3 0 1.02947485.5215457 1.96853646 1.3698342 2.51900785l.6301658.40892721v1.02400184l-.79002171.3290552c-1.93395773.8055207-3.20997829 2.7024791-3.20997829 4.8180274z" fill-rule="evenodd"/></symbol><symbol id="icon-email" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-.0049107 2.55749512v1.44250488l-7 4-7-4v-1.44250488l7 4z" fill-rule="evenodd"/></symbol><symbol id="icon-error" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm2.8630343 4.71100931-2.8630343 2.86303426-2.86303426-2.86303426c-.39658757-.39658757-1.03281091-.39438847-1.4265779-.00062147-.39651227.39651226-.39348876 1.03246767.00062147 1.4265779l2.86303426 2.86303426-2.86303426 2.8630343c-.39658757.3965875-.39438847 1.0328109-.00062147 1.4265779.39651226.3965122 1.03246767.3934887 1.4265779-.0006215l2.86303426-2.8630343 2.8630343 2.8630343c.3965875.3965876 1.0328109.3943885 1.4265779.0006215.3965122-.3965123.3934887-1.0324677-.0006215-1.4265779l-2.8630343-2.8630343 2.8630343-2.86303426c.3965876-.39658757.3943885-1.03281091.0006215-1.4265779-.3965123-.39651227-1.0324677-.39348876-1.4265779.00062147z" fill-rule="evenodd"/></symbol><symbol id="icon-ethics" viewBox="0 0 18 18"><path d="m6.76384967 1.41421356.83301651-.8330165c.77492941-.77492941 2.03133823-.77492941 2.80626762 0l.8330165.8330165c.3750728.37507276.8837806.58578644 1.4142136.58578644h1.3496361c1.1045695 0 2 .8954305 2 2v1.34963611c0 .53043298.2107137 1.03914081.5857864 1.41421356l.8330165.83301651c.7749295.77492941.7749295 2.03133823 0 2.80626762l-.8330165.8330165c-.3750727.3750728-.5857864.8837806-.5857864 1.4142136v1.3496361c0 1.1045695-.8954305 2-2 2h-1.3496361c-.530433 0-1.0391408.2107137-1.4142136.5857864l-.8330165.8330165c-.77492939.7749295-2.03133821.7749295-2.80626762 0l-.83301651-.8330165c-.37507275-.3750727-.88378058-.5857864-1.41421356-.5857864h-1.34963611c-1.1045695 0-2-.8954305-2-2v-1.3496361c0-.530433-.21071368-1.0391408-.58578644-1.4142136l-.8330165-.8330165c-.77492941-.77492939-.77492941-2.03133821 0-2.80626762l.8330165-.83301651c.37507276-.37507275.58578644-.88378058.58578644-1.41421356v-1.34963611c0-1.1045695.8954305-2 2-2h1.34963611c.53043298 0 1.03914081-.21071368 1.41421356-.58578644zm-1.41421356 1.58578644h-1.34963611c-.55228475 0-1 .44771525-1 1v1.34963611c0 .79564947-.31607052 1.55871121-.87867966 2.12132034l-.8330165.83301651c-.38440512.38440512-.38440512 1.00764896 0 1.39205408l.8330165.83301646c.56260914.5626092.87867966 1.3256709.87867966 2.1213204v1.3496361c0 .5522847.44771525 1 1 1h1.34963611c.79564947 0 1.55871121.3160705 2.12132034.8786797l.83301651.8330165c.38440512.3844051 1.00764896.3844051 1.39205408 0l.83301646-.8330165c.5626092-.5626092 1.3256709-.8786797 2.1213204-.8786797h1.3496361c.5522847 0 1-.4477153 1-1v-1.3496361c0-.7956495.3160705-1.5587112.8786797-2.1213204l.8330165-.83301646c.3844051-.38440512.3844051-1.00764896 0-1.39205408l-.8330165-.83301651c-.5626092-.56260913-.8786797-1.32567087-.8786797-2.12132034v-1.34963611c0-.55228475-.4477153-1-1-1h-1.3496361c-.7956495 0-1.5587112-.31607052-2.1213204-.87867966l-.83301646-.8330165c-.38440512-.38440512-1.00764896-.38440512-1.39205408 0l-.83301651.8330165c-.56260913.56260914-1.32567087.87867966-2.12132034.87867966zm3.58698944 11.4960218c-.02081224.002155-.04199226.0030286-.06345763.002542-.98766446-.0223875-1.93408568-.3063547-2.75885125-.8155622-.23496767-.1450683-.30784554-.4531483-.16277726-.688116.14506827-.2349677.45314827-.3078455.68811595-.1627773.67447084.4164161 1.44758575.6483839 2.25617384.6667123.01759529.0003988.03495764.0017019.05204365.0038639.01713363-.0017748.03452416-.0026845.05212715-.0026845 2.4852814 0 4.5-2.0147186 4.5-4.5 0-1.04888973-.3593547-2.04134635-1.0074477-2.83787157-.1742817-.21419731-.1419238-.5291218.0722736-.70340353.2141973-.17428173.5291218-.14192375.7034035.07227357.7919032.97327203 1.2317706 2.18808682 1.2317706 3.46900153 0 3.0375661-2.4624339 5.5-5.5 5.5-.02146768 0-.04261937-.0013529-.06337445-.0039782zm1.57975095-10.78419583c.2654788.07599731.419084.35281842.3430867.61829728-.0759973.26547885-.3528185.419084-.6182973.3430867-.37560116-.10752146-.76586237-.16587951-1.15568824-.17249193-2.5587807-.00064534-4.58547766 2.00216524-4.58547766 4.49928198 0 .62691557.12797645 1.23496.37274865 1.7964426.11035133.2531347-.0053975.5477984-.25853224.6581497-.25313473.1103514-.54779841-.0053975-.65814974-.2585322-.29947131-.6869568-.45606667-1.43097603-.45606667-2.1960601 0-3.05211432 2.47714695-5.50006595 5.59399617-5.49921198.48576182.00815502.96289603.0795037 1.42238033.21103795zm-1.9766658 6.41091303 2.69835-2.94655317c.1788432-.21040373.4943901-.23598862.7047939-.05714545.2104037.17884318.2359886.49439014.0571454.70479387l-3.01637681 3.34277395c-.18039088.1999106-.48669547.2210637-.69285412.0478478l-1.93095347-1.62240047c-.21213845-.17678204-.24080048-.49206439-.06401844-.70420284.17678204-.21213844.49206439-.24080048.70420284-.06401844z" fill-rule="evenodd"/></symbol><symbol id="icon-expand"><path d="M7.498 11.918a.997.997 0 0 0-.003-1.411.995.995 0 0 0-1.412-.003l-4.102 4.102v-3.51A1 1 0 0 0 .98 10.09.992.992 0 0 0 0 11.092V17c0 .554.448 1.002 1.002 1.002h5.907c.554 0 1.002-.45 1.002-1.003 0-.539-.45-.978-1.006-.978h-3.51zm3.005-5.835a.997.997 0 0 0 .003 1.412.995.995 0 0 0 1.411.003l4.103-4.103v3.51a1 1 0 0 0 1.001 1.006A.992.992 0 0 0 18 6.91V1.002A1 1 0 0 0 17 0h-5.907a1.003 1.003 0 0 0-1.002 1.003c0 .539.45.978 1.006.978h3.51z" fill-rule="evenodd"/></symbol><symbol id="icon-explore" viewBox="0 0 18 18"><path d="m9 17c4.418278 0 8-3.581722 8-8s-3.581722-8-8-8-8 3.581722-8 8 3.581722 8 8 8zm0 1c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9zm0-2.5c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5c2.969509 0 5.400504-2.3575119 5.497023-5.31714844.0090007-.27599565.2400359-.49243782.5160315-.48343711.2759957.0090007.4924378.2400359.4834371.51603155-.114093 3.4985237-2.9869632 6.284554-6.4964916 6.284554zm-.29090657-12.99359748c.27587424-.01216621.50937715.20161139.52154336.47748563.01216621.27587423-.20161139.50937715-.47748563.52154336-2.93195733.12930094-5.25315116 2.54886451-5.25315116 5.49456849 0 .27614237-.22385763.5-.5.5s-.5-.22385763-.5-.5c0-3.48142406 2.74307146-6.34074398 6.20909343-6.49359748zm1.13784138 8.04763908-1.2004882-1.20048821c-.19526215-.19526215-.19526215-.51184463 0-.70710678s.51184463-.19526215.70710678 0l1.20048821 1.2004882 1.6006509-4.00162734-4.50670359 1.80268144-1.80268144 4.50670359zm4.10281269-6.50378907-2.6692597 6.67314927c-.1016411.2541026-.3029834.4554449-.557086.557086l-6.67314927 2.6692597 2.66925969-6.67314926c.10164107-.25410266.30298336-.45544495.55708602-.55708602z" fill-rule="evenodd"/></symbol><symbol id="icon-filter" viewBox="0 0 16 16"><path d="m14.9738641 0c.5667192 0 1.0261359.4477136 1.0261359 1 0 .24221858-.0902161.47620768-.2538899.65849851l-5.6938314 6.34147206v5.49997973c0 .3147562-.1520673.6111434-.4104543.7999971l-2.05227171 1.4999945c-.45337535.3313696-1.09655869.2418269-1.4365902-.1999993-.13321514-.1730955-.20522717-.3836284-.20522717-.5999978v-6.99997423l-5.69383133-6.34147206c-.3731872-.41563511-.32996891-1.0473954.09653074-1.41107611.18705584-.15950448.42716133-.2474224.67571519-.2474224zm-5.9218641 8.5h-2.105v6.491l.01238459.0070843.02053271.0015705.01955278-.0070558 2.0532976-1.4990996zm-8.02585008-7.5-.01564945.00240169 5.83249953 6.49759831h2.313l5.836-6.499z"/></symbol><symbol id="icon-home" viewBox="0 0 18 18"><path d="m9 5-6 6v5h4v-4h4v4h4v-5zm7 6.5857864v4.4142136c0 .5522847-.4477153 1-1 1h-5v-4h-2v4h-5c-.55228475 0-1-.4477153-1-1v-4.4142136c-.25592232 0-.51184464-.097631-.70710678-.2928932l-.58578644-.5857864c-.39052429-.3905243-.39052429-1.02368929 0-1.41421358l8.29289322-8.29289322 8.2928932 8.29289322c.3905243.39052429.3905243 1.02368928 0 1.41421358l-.5857864.5857864c-.1952622.1952622-.4511845.2928932-.7071068.2928932zm-7-9.17157284-7.58578644 7.58578644.58578644.5857864 7-6.99999996 7 6.99999996.5857864-.5857864z" fill-rule="evenodd"/></symbol><symbol id="icon-image" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm-3.49645283 10.1752453-3.89407257 6.7495552c.11705545.048464.24538859.0751995.37998328.0751995h10.60290092l-2.4329715-4.2154691-1.57494129 2.7288098zm8.49779013 6.8247547c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v13.98991071l4.50814957-7.81026689 3.08089884 5.33809539 1.57494129-2.7288097 3.5875735 6.2159812zm-3.0059397-11c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2-2-.8954305-2-2 .8954305-2 2-2zm0 1c-.5522847 0-1 .44771525-1 1s.4477153 1 1 1 1-.44771525 1-1-.4477153-1-1-1z" fill-rule="evenodd"/></symbol><symbol id="icon-info" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm0 7h-1.5l-.11662113.00672773c-.49733868.05776511-.88337887.48043643-.88337887.99327227 0 .47338693.32893365.86994729.77070917.97358929l.1126697.01968298.11662113.00672773h.5v3h-.5l-.11662113.0067277c-.42082504.0488782-.76196299.3590206-.85696816.7639815l-.01968298.1126697-.00672773.1166211.00672773.1166211c.04887817.4208251.35902055.761963.76398144.8569682l.1126697.019683.11662113.0067277h3l.1166211-.0067277c.4973387-.0577651.8833789-.4804365.8833789-.9932723 0-.4733869-.3289337-.8699473-.7707092-.9735893l-.1126697-.019683-.1166211-.0067277h-.5v-4l-.00672773-.11662113c-.04887817-.42082504-.35902055-.76196299-.76398144-.85696816l-.1126697-.01968298zm0-3.25c-.69035594 0-1.25.55964406-1.25 1.25s.55964406 1.25 1.25 1.25 1.25-.55964406 1.25-1.25-.55964406-1.25-1.25-1.25z" fill-rule="evenodd"/></symbol><symbol id="icon-institution" viewBox="0 0 18 18"><path d="m7 16.9998189v-2.0003623h4v2.0003623h2v-3.0005434h-8v3.0005434zm-3-10.00181122h-1.52632364c-.27614237 0-.5-.22389817-.5-.50009056 0-.13995446.05863589-.27350497.16166338-.36820841l1.23156713-1.13206327h-2.36690687v12.00217346h3v-2.0003623h-3v-1.0001811h3v-1.0001811h1v-4.00072448h-1zm10 0v2.00036224h-1v4.00072448h1v1.0001811h3v1.0001811h-3v2.0003623h3v-12.00217346h-2.3695309l1.2315671 1.13206327c.2033191.186892.2166633.50325042.0298051.70660631-.0946863.10304615-.2282126.16169266-.3681417.16169266zm3-3.00054336c.5522847 0 1 .44779634 1 1.00018112v13.00235456h-18v-13.00235456c0-.55238478.44771525-1.00018112 1-1.00018112h3.45499992l4.20535144-3.86558216c.19129876-.17584288.48537447-.17584288.67667324 0l4.2053514 3.86558216zm-4 3.00054336h-8v1.00018112h8zm-2 6.00108672h1v-4.00072448h-1zm-1 0v-4.00072448h-2v4.00072448zm-3 0v-4.00072448h-1v4.00072448zm8-4.00072448c.5522847 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.4477153-1.00018112 1-1.00018112zm-12 0c.55228475 0 1 .44779634 1 1.00018112v2.00036226h-2v-2.00036226c0-.55238478.44771525-1.00018112 1-1.00018112zm5.99868798-7.81907007-5.24205601 4.81852671h10.48411203zm.00131202 3.81834559c-.55228475 0-1-.44779634-1-1.00018112s.44771525-1.00018112 1-1.00018112 1 .44779634 1 1.00018112-.44771525 1.00018112-1 1.00018112zm-1 11.00199236v1.0001811h2v-1.0001811z" fill-rule="evenodd"/></symbol><symbol id="icon-location" viewBox="0 0 18 18"><path d="m9.39521328 16.2688008c.79596342-.7770119 1.59208152-1.6299956 2.33285652-2.5295081 1.4020032-1.7024324 2.4323601-3.3624519 2.9354918-4.871847.2228715-.66861448.3364384-1.29323246.3364384-1.8674457 0-3.3137085-2.6862915-6-6-6-3.36356866 0-6 2.60156856-6 6 0 .57421324.11356691 1.19883122.3364384 1.8674457.50313169 1.5093951 1.53348863 3.1694146 2.93549184 4.871847.74077492.8995125 1.53689309 1.7524962 2.33285648 2.5295081.13694479.1336842.26895677.2602648.39521328.3793207.12625651-.1190559.25826849-.2456365.39521328-.3793207zm-.39521328 1.7311992s-7-6-7-11c0-4 3.13400675-7 7-7 3.8659932 0 7 3.13400675 7 7 0 5-7 11-7 11zm0-8c-1.65685425 0-3-1.34314575-3-3s1.34314575-3 3-3c1.6568542 0 3 1.34314575 3 3s-1.3431458 3-3 3zm0-1c1.1045695 0 2-.8954305 2-2s-.8954305-2-2-2-2 .8954305-2 2 .8954305 2 2 2z" fill-rule="evenodd"/></symbol><symbol id="icon-minus" viewBox="0 0 16 16"><path d="m2.00087166 7h11.99825664c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-11.99825664c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-newsletter" viewBox="0 0 18 18"><path d="m9 11.8482489 2-1.1428571v-1.7053918h-4v1.7053918zm-3-1.7142857v-2.1339632h6v2.1339632l3-1.71428574v-6.41967746h-12v6.41967746zm10-5.3839632 1.5299989.95624934c.2923814.18273835.4700011.50320827.4700011.8479983v8.44575236c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-8.44575236c0-.34479003.1776197-.66525995.47000106-.8479983l1.52999894-.95624934v-2.75c0-.55228475.44771525-1 1-1h12c.5522847 0 1 .44771525 1 1zm0 1.17924764v3.07075236l-7 4-7-4v-3.07075236l-1 .625v8.44575236c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-8.44575236zm-10-1.92924764h6v1h-6zm-1 2h8v1h-8z" fill-rule="evenodd"/></symbol><symbol id="icon-orcid" viewBox="0 0 18 18"><path d="m9 1c4.418278 0 8 3.581722 8 8s-3.581722 8-8 8-8-3.581722-8-8 3.581722-8 8-8zm-2.90107518 5.2732337h-1.41865256v7.1712107h1.41865256zm4.55867178.02508949h-2.99247027v7.14612121h2.91062487c.7673039 0 1.4476365-.1483432 2.0410182-.445034s1.0511995-.7152915 1.3734671-1.2558144c.3222677-.540523.4833991-1.1603247.4833991-1.85942385 0-.68545815-.1602789-1.30270225-.4808414-1.85175082-.3205625-.54904856-.7707074-.97532211-1.3504481-1.27883343-.5797408-.30351132-1.2413173-.45526471-1.9847495-.45526471zm-.1892674 1.07933542c.7877654 0 1.4143875.22336734 1.8798852.67010873.4654977.44674138.698243 1.05546001.698243 1.82617415 0 .74343221-.2310402 1.34447791-.6931277 1.80315511-.4620874.4586773-1.0750688.6880124-1.8389625.6880124h-1.46810075v-4.98745039zm-5.08652545-3.71099194c-.21825533 0-.410525.08444276-.57681478.25333081-.16628977.16888806-.24943341.36245684-.24943341.58071218 0 .22345188.08314364.41961891.24943341.58850696.16628978.16888806.35855945.25333082.57681478.25333082.233845 0 .43390938-.08314364.60019916-.24943342.16628978-.16628977.24943342-.36375592.24943342-.59240436 0-.233845-.08314364-.43131115-.24943342-.59240437s-.36635416-.24163862-.60019916-.24163862z" fill-rule="evenodd"/></symbol><symbol id="icon-plus" viewBox="0 0 16 16"><path d="m2.00087166 7h4.99912834v-4.99912834c0-.55276616.44386482-1.00087166 1-1.00087166.55228475 0 1 .44463086 1 1.00087166v4.99912834h4.9991283c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-4.9991283v4.9991283c0 .5527662-.44386482 1.0008717-1 1.0008717-.55228475 0-1-.4446309-1-1.0008717v-4.9991283h-4.99912834c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-print" viewBox="0 0 18 18"><path d="m16.0049107 5h-14.00982141c-.54941618 0-.99508929.4467783-.99508929.99961498v6.00077002c0 .5570958.44271433.999615.99508929.999615h1.00491071v-3h12v3h1.0049107c.5494162 0 .9950893-.4467783.9950893-.999615v-6.00077002c0-.55709576-.4427143-.99961498-.9950893-.99961498zm-2.0049107-1v-2.00208688c0-.54777062-.4519464-.99791312-1.0085302-.99791312h-7.9829396c-.55661731 0-1.0085302.44910695-1.0085302.99791312v2.00208688zm1 10v2.0018986c0 1.103521-.9019504 1.9981014-2.0085302 1.9981014h-7.9829396c-1.1092806 0-2.0085302-.8867064-2.0085302-1.9981014v-2.0018986h-1.00491071c-1.10185739 0-1.99508929-.8874333-1.99508929-1.999615v-6.00077002c0-1.10435686.8926228-1.99961498 1.99508929-1.99961498h1.00491071v-2.00208688c0-1.10341695.90195036-1.99791312 2.0085302-1.99791312h7.9829396c1.1092806 0 2.0085302.89826062 2.0085302 1.99791312v2.00208688h1.0049107c1.1018574 0 1.9950893.88743329 1.9950893 1.99961498v6.00077002c0 1.1043569-.8926228 1.999615-1.9950893 1.999615zm-1-3h-10v5.0018986c0 .5546075.44702548.9981014 1.0085302.9981014h7.9829396c.5565964 0 1.0085302-.4491701 1.0085302-.9981014zm-9 1h8v1h-8zm0 2h5v1h-5zm9-5c-.5522847 0-1-.44771525-1-1s.4477153-1 1-1 1 .44771525 1 1-.4477153 1-1 1z" fill-rule="evenodd"/></symbol><symbol id="icon-search" viewBox="0 0 22 22"><path d="M21.697 20.261a1.028 1.028 0 01.01 1.448 1.034 1.034 0 01-1.448-.01l-4.267-4.267A9.812 9.811 0 010 9.812a9.812 9.811 0 1117.43 6.182zM9.812 18.222A8.41 8.41 0 109.81 1.403a8.41 8.41 0 000 16.82z" fill-rule="evenodd"/></symbol><symbol id="icon-social-facebook" viewBox="0 0 24 24"><path d="m6.00368507 20c-1.10660471 0-2.00368507-.8945138-2.00368507-1.9940603v-12.01187942c0-1.10128908.89451376-1.99406028 1.99406028-1.99406028h12.01187942c1.1012891 0 1.9940603.89451376 1.9940603 1.99406028v12.01187942c0 1.1012891-.88679 1.9940603-2.0032184 1.9940603h-2.9570132v-6.1960818h2.0797387l.3114113-2.414723h-2.39115v-1.54164807c0-.69911803.1941355-1.1755439 1.1966615-1.1755439l1.2786739-.00055875v-2.15974763l-.2339477-.02492088c-.3441234-.03134957-.9500153-.07025255-1.6293054-.07025255-1.8435726 0-3.1057323 1.12531866-3.1057323 3.19187953v1.78079225h-2.0850778v2.414723h2.0850778v6.1960818z" fill-rule="evenodd"/></symbol><symbol id="icon-social-twitter" viewBox="0 0 24 24"><path d="m18.8767135 6.87445248c.7638174-.46908424 1.351611-1.21167363 1.6250764-2.09636345-.7135248.43394112-1.50406.74870123-2.3464594.91677702-.6695189-.73342162-1.6297913-1.19486605-2.6922204-1.19486605-2.0399895 0-3.6933555 1.69603749-3.6933555 3.78628909 0 .29642457.0314329.58673729.0942985.8617704-3.06469922-.15890802-5.78835241-1.66547825-7.60988389-3.9574208-.3174714.56076194-.49978171 1.21167363-.49978171 1.90536824 0 1.31404706.65223085 2.47224203 1.64236444 3.15218497-.60350999-.0198635-1.17401554-.1925232-1.67222562-.47366811v.04583885c0 1.83355406 1.27302891 3.36609966 2.96411421 3.71294696-.31118484.0886217-.63651445.1329326-.97441718.1329326-.2357461 0-.47149219-.0229194-.69466516-.0672303.47149219 1.5065703 1.83253297 2.6036468 3.44975116 2.632678-1.2651707 1.0160946-2.85724264 1.6196394-4.5891906 1.6196394-.29861172 0-.59093688-.0152796-.88011875-.0504227 1.63450624 1.0726291 3.57548241 1.6990934 5.66104951 1.6990934 6.79263079 0 10.50641749-5.7711113 10.50641749-10.7751859l-.0094298-.48894775c.7229547-.53478659 1.3516109-1.20250585 1.8419628-1.96190282-.6632323.30100846-1.3751855.50422736-2.1217148.59590507z" fill-rule="evenodd"/></symbol><symbol id="icon-social-youtube" viewBox="0 0 24 24"><path d="m10.1415 14.3973208-.0005625-5.19318431 4.863375 2.60554491zm9.963-7.92753362c-.6845625-.73643756-1.4518125-.73990314-1.803375-.7826454-2.518875-.18714178-6.2971875-.18714178-6.2971875-.18714178-.007875 0-3.7861875 0-6.3050625.18714178-.352125.04274226-1.1188125.04620784-1.8039375.7826454-.5394375.56084773-.7149375 1.8344515-.7149375 1.8344515s-.18 1.49597903-.18 2.99138042v1.4024082c0 1.495979.18 2.9913804.18 2.9913804s.1755 1.2736038.7149375 1.8344515c.685125.7364376 1.5845625.7133337 1.9850625.7901542 1.44.1420891 6.12.1859866 6.12.1859866s3.78225-.005776 6.301125-.1929178c.3515625-.0433198 1.1188125-.0467854 1.803375-.783223.5394375-.5608477.7155-1.8344515.7155-1.8344515s.18-1.4954014.18-2.9913804v-1.4024082c0-1.49540139-.18-2.99138042-.18-2.99138042s-.1760625-1.27360377-.7155-1.8344515z" fill-rule="evenodd"/></symbol><symbol id="icon-subject-medicine" viewBox="0 0 18 18"><path d="m12.5 8h-6.5c-1.65685425 0-3 1.34314575-3 3v1c0 1.6568542 1.34314575 3 3 3h1v-2h-.5c-.82842712 0-1.5-.6715729-1.5-1.5s.67157288-1.5 1.5-1.5h1.5 2 1 2c1.6568542 0 3-1.34314575 3-3v-1c0-1.65685425-1.3431458-3-3-3h-2v2h1.5c.8284271 0 1.5.67157288 1.5 1.5s-.6715729 1.5-1.5 1.5zm-5.5-1v-1h-3.5c-1.38071187 0-2.5-1.11928813-2.5-2.5s1.11928813-2.5 2.5-2.5h1.02786405c.46573528 0 .92507448.10843528 1.34164078.31671843l1.13382424.56691212c.06026365-1.05041141.93116291-1.88363055 1.99667093-1.88363055 1.1045695 0 2 .8954305 2 2h2c2.209139 0 4 1.790861 4 4v1c0 2.209139-1.790861 4-4 4h-2v1h2c1.1045695 0 2 .8954305 2 2s-.8954305 2-2 2h-2c0 1.1045695-.8954305 2-2 2s-2-.8954305-2-2h-1c-2.209139 0-4-1.790861-4-4v-1c0-2.209139 1.790861-4 4-4zm0-2v-2.05652691c-.14564246-.03538148-.28733393-.08714006-.42229124-.15461871l-1.15541752-.57770876c-.27771087-.13885544-.583937-.21114562-.89442719-.21114562h-1.02786405c-.82842712 0-1.5.67157288-1.5 1.5s.67157288 1.5 1.5 1.5zm4 1v1h1.5c.2761424 0 .5-.22385763.5-.5s-.2238576-.5-.5-.5zm-1 1v-5c0-.55228475-.44771525-1-1-1s-1 .44771525-1 1v5zm-2 4v5c0 .5522847.44771525 1 1 1s1-.4477153 1-1v-5zm3 2v2h2c.5522847 0 1-.4477153 1-1s-.4477153-1-1-1zm-4-1v-1h-.5c-.27614237 0-.5.2238576-.5.5s.22385763.5.5.5zm-3.5-9h1c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5z" fill-rule="evenodd"/></symbol><symbol id="icon-success" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm3.4860198 4.98163161-4.71802968 5.50657859-2.62834168-2.02300024c-.42862421-.36730544-1.06564993-.30775346-1.42283677.13301307-.35718685.44076653-.29927542 1.0958383.12934879 1.46314377l3.40735508 2.7323063c.42215801.3385221 1.03700951.2798252 1.38749189-.1324571l5.38450527-6.33394549c.3613513-.43716226.3096573-1.09278382-.115462-1.46437175-.4251192-.37158792-1.0626796-.31842941-1.4240309.11873285z" fill-rule="evenodd"/></symbol><symbol id="icon-table" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587l-4.0059107-.001.001.001h-1l-.001-.001h-5l.001.001h-1l-.001-.001-3.00391071.001c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm-11.0059107 5h-3.999v6.9941413c0 .5572961.44630695 1.0058587.99508929 1.0058587h3.00391071zm6 0h-5v8h5zm5.0059107-4h-4.0059107v3h5.001v1h-5.001v7.999l4.0059107.001c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-12.5049107 9c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.2238576.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.2238576-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.2238576.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.2238576-.5-.5s.22385763-.5.5-.5zm-6-2c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-1c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm12 0c.2761424 0 .5.22385763.5.5s-.2238576.5-.5.5h-2c-.2761424 0-.5-.22385763-.5-.5s.2238576-.5.5-.5zm-6 0c.27614237 0 .5.22385763.5.5s-.22385763.5-.5.5h-2c-.27614237 0-.5-.22385763-.5-.5s.22385763-.5.5-.5zm1.499-5h-5v3h5zm-6 0h-3.00391071c-.54871518 0-.99508929.44887827-.99508929 1.00585866v1.99414134h3.999z" fill-rule="evenodd"/></symbol><symbol id="icon-tick-circle" viewBox="0 0 24 24"><path d="m12 2c5.5228475 0 10 4.4771525 10 10s-4.4771525 10-10 10-10-4.4771525-10-10 4.4771525-10 10-10zm0 1c-4.97056275 0-9 4.02943725-9 9 0 4.9705627 4.02943725 9 9 9 4.9705627 0 9-4.0294373 9-9 0-4.97056275-4.0294373-9-9-9zm4.2199868 5.36606669c.3613514-.43716226.9989118-.49032077 1.424031-.11873285s.4768133 1.02720949.115462 1.46437175l-6.093335 6.94397871c-.3622945.4128716-.9897871.4562317-1.4054264.0971157l-3.89719065-3.3672071c-.42862421-.3673054-.48653564-1.0223772-.1293488-1.4631437s.99421256-.5003185 1.42283677-.1330131l3.11097438 2.6987741z" fill-rule="evenodd"/></symbol><symbol id="icon-tick" viewBox="0 0 16 16"><path d="m6.76799012 9.21106946-3.1109744-2.58349728c-.42862421-.35161617-1.06564993-.29460792-1.42283677.12733148s-.29927541 1.04903009.1293488 1.40064626l3.91576307 3.23873978c.41034319.3393961 1.01467563.2976897 1.37450571-.0948578l6.10568327-6.660841c.3613513-.41848908.3096572-1.04610608-.115462-1.4018218-.4251192-.35571573-1.0626796-.30482786-1.424031.11366122z" fill-rule="evenodd"/></symbol><symbol id="icon-update" viewBox="0 0 18 18"><path d="m1 13v1c0 .5522847.44771525 1 1 1h14c.5522847 0 1-.4477153 1-1v-1h-1v-10h-14v10zm16-1h1v2c0 1.1045695-.8954305 2-2 2h-14c-1.1045695 0-2-.8954305-2-2v-2h1v-9c0-.55228475.44771525-1 1-1h14c.5522847 0 1 .44771525 1 1zm-1 0v1h-4.5857864l-1 1h-2.82842716l-1-1h-4.58578644v-1h5l1 1h2l1-1zm-13-8h12v7h-12zm1 1v5h10v-5zm1 1h4v1h-4zm0 2h4v1h-4z" fill-rule="evenodd"/></symbol><symbol id="icon-upload" viewBox="0 0 18 18"><path d="m10.0046024 0c.5497429 0 1.3179837.32258606 1.707238.71184039l4.5763192 4.57631922c.3931386.39313859.7118404 1.16760135.7118404 1.71431368v8.98899651c0 1.1092806-.8945138 2.0085302-1.9940603 2.0085302h-12.01187942c-1.10128908 0-1.99406028-.8926228-1.99406028-1.9950893v-14.00982141c0-1.10185739.88743329-1.99508929 1.99961498-1.99508929zm0 1h-7.00498742c-.55709576 0-.99961498.44271433-.99961498.99508929v14.00982141c0 .5500396.44491393.9950893.99406028.9950893h12.01187942c.5463747 0 .9940603-.4506622.9940603-1.0085302v-8.98899651c0-.28393444-.2150684-.80332809-.4189472-1.0072069l-4.5763192-4.57631922c-.2038461-.20384606-.718603-.41894717-1.0001312-.41894717zm-1.85576936 4.14572769c.19483374-.19483375.51177826-.19377714.70556874.00001334l2.59099082 2.59099079c.1948411.19484112.1904373.51514474.0027906.70279143-.1932998.19329987-.5046517.19237083-.7001856-.00692852l-1.74638687-1.7800176v6.14827687c0 .2717771-.23193359.492096-.5.492096-.27614237 0-.5-.216372-.5-.492096v-6.14827641l-1.74627892 1.77990922c-.1933927.1971171-.51252214.19455839-.70016883.0069117-.19329987-.19329988-.19100584-.50899493.00277731-.70277808z" fill-rule="evenodd"/></symbol><symbol id="icon-video" viewBox="0 0 18 18"><path d="m16.0049107 2c1.1018574 0 1.9950893.89706013 1.9950893 2.00585866v9.98828264c0 1.1078052-.8926228 2.0058587-1.9950893 2.0058587h-14.00982141c-1.10185739 0-1.99508929-.8970601-1.99508929-2.0058587v-9.98828264c0-1.10780515.8926228-2.00585866 1.99508929-2.00585866zm0 1h-14.00982141c-.54871518 0-.99508929.44887827-.99508929 1.00585866v9.98828264c0 .5572961.44630695 1.0058587.99508929 1.0058587h14.00982141c.5487152 0 .9950893-.4488783.9950893-1.0058587v-9.98828264c0-.55729607-.446307-1.00585866-.9950893-1.00585866zm-8.30912922 2.24944486 4.60460462 2.73982242c.9365543.55726659.9290753 1.46522435 0 2.01804082l-4.60460462 2.7398224c-.93655425.5572666-1.69578148.1645632-1.69578148-.8937585v-5.71016863c0-1.05087579.76670616-1.446575 1.69578148-.89375851zm-.67492769.96085624v5.5750128c0 .2995102-.10753745.2442517.16578928.0847713l4.58452283-2.67497259c.3050619-.17799716.3051624-.21655446 0-.39461026l-4.58452283-2.67497264c-.26630747-.15538481-.16578928-.20699944-.16578928.08477139z" fill-rule="evenodd"/></symbol><symbol id="icon-warning" viewBox="0 0 18 18"><path d="m9 11.75c.69035594 0 1.25.5596441 1.25 1.25s-.55964406 1.25-1.25 1.25-1.25-.5596441-1.25-1.25.55964406-1.25 1.25-1.25zm.41320045-7.75c.55228475 0 1.00000005.44771525 1.00000005 1l-.0034543.08304548-.3333333 4c-.043191.51829212-.47645714.91695452-.99654578.91695452h-.15973424c-.52008864 0-.95335475-.3986624-.99654576-.91695452l-.33333333-4c-.04586475-.55037702.36312325-1.03372649.91350028-1.07959124l.04148683-.00259031zm-.41320045 14c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-checklist-banner" viewBox="0 0 56.69 56.69"><path style="fill:none" d="M0 0h56.69v56.69H0z"/><clipPath id="b"><use xlink:href="#a" style="overflow:visible"/></clipPath><path d="M21.14 34.46c0-6.77 5.48-12.26 12.24-12.26s12.24 5.49 12.24 12.26-5.48 12.26-12.24 12.26c-6.76-.01-12.24-5.49-12.24-12.26zm19.33 10.66 10.23 9.22s1.21 1.09 2.3-.12l2.09-2.32s1.09-1.21-.12-2.3l-10.23-9.22m-19.29-5.92c0-4.38 3.55-7.94 7.93-7.94s7.93 3.55 7.93 7.94c0 4.38-3.55 7.94-7.93 7.94-4.38-.01-7.93-3.56-7.93-7.94zm17.58 12.99 4.14-4.81" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round"/><path d="M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5m14.42-5.2V4.86s0-2.93-2.93-2.93H4.13s-2.93 0-2.93 2.93v37.57s0 2.93 2.93 2.93h15.01M8.26 9.75H28.6M8.26 15.98H28.6m-20.34 6.2h12.5" style="clip-path:url(#b);fill:none;stroke:#01324b;stroke-width:2;stroke-linecap:round;stroke-linejoin:round"/></symbol><symbol id="icon-chevron-down" viewBox="0 0 16 16"><path d="m5.58578644 3-3.29289322-3.29289322c-.39052429-.39052429-.39052429-1.02368927 0-1.41421356s1.02368927-.39052429 1.41421356 0l4 4c.39052429.39052429.39052429 1.02368927 0 1.41421356l-4 4c-.39052429.39052429-1.02368927.39052429-1.41421356 0s-.39052429-1.02368927 0-1.41421356z" fill-rule="evenodd" transform="matrix(0 1 -1 0 11 1)"/></symbol><symbol id="icon-eds-i-arrow-right-medium" viewBox="0 0 24 24"><path d="m12.728 3.293 7.98 7.99a.996.996 0 0 1 .281.561l.011.157c0 .32-.15.605-.384.788l-7.908 7.918a1 1 0 0 1-1.416-1.414L17.576 13H4a1 1 0 0 1 0-2h13.598l-6.285-6.293a1 1 0 0 1-.082-1.32l.083-.095a1 1 0 0 1 1.414.001Z"/></symbol><symbol id="icon-eds-i-chevron-down-medium" viewBox="0 0 16 16"><path d="m2.00087166 7h4.99912834v-4.99912834c0-.55276616.44386482-1.00087166 1-1.00087166.55228475 0 1 .44463086 1 1.00087166v4.99912834h4.9991283c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-4.9991283v4.9991283c0 .5527662-.44386482 1.0008717-1 1.0008717-.55228475 0-1-.4446309-1-1.0008717v-4.9991283h-4.99912834c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-chevron-down-small" viewBox="0 0 16 16"><path d="M13.692 5.278a1 1 0 0 1 .03 1.414L9.103 11.51a1.491 1.491 0 0 1-2.188.019L2.278 6.692a1 1 0 0 1 1.444-1.384L8 9.771l4.278-4.463a1 1 0 0 1 1.318-.111l.096.081Z"/></symbol><symbol id="icon-eds-i-chevron-right-medium" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-eds-i-chevron-right-small" viewBox="0 0 10 10"><path d="m5.96738168 4.70639573 2.39518594-2.41447274c.37913917-.38219212.98637524-.38972225 1.35419292-.01894278.37750606.38054586.37784436.99719163-.00013556 1.37821513l-4.03074001 4.06319683c-.37758093.38062133-.98937525.38100976-1.367372-.00003075l-4.03091981-4.06337806c-.37759778-.38063832-.38381821-.99150444-.01600053-1.3622839.37750607-.38054587.98772445-.38240057 1.37006824.00302197l2.39538588 2.4146743.96295325.98624457z" fill-rule="evenodd" transform="matrix(0 -1 1 0 0 10)"/></symbol><symbol id="icon-eds-i-chevron-up-medium" viewBox="0 0 16 16"><path d="m2.00087166 7h11.99825664c.5527662 0 1.0008717.44386482 1.0008717 1 0 .55228475-.4446309 1-1.0008717 1h-11.99825664c-.55276616 0-1.00087166-.44386482-1.00087166-1 0-.55228475.44463086-1 1.00087166-1z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-close-medium" viewBox="0 0 16 16"><path d="m2.29679575 12.2772478c-.39658757.3965876-.39438847 1.0328109-.00062148 1.4265779.39651227.3965123 1.03246768.3934888 1.42657791-.0006214l4.27724782-4.27724787 4.2772478 4.27724787c.3965876.3965875 1.0328109.3943884 1.4265779.0006214.3965123-.3965122.3934888-1.0324677-.0006214-1.4265779l-4.27724787-4.2772478 4.27724787-4.27724782c.3965875-.39658757.3943884-1.03281091.0006214-1.42657791-.3965122-.39651226-1.0324677-.39348875-1.4265779.00062148l-4.2772478 4.27724782-4.27724782-4.27724782c-.39658757-.39658757-1.03281091-.39438847-1.42657791-.00062148-.39651226.39651227-.39348875 1.03246768.00062148 1.42657791l4.27724782 4.27724782z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-download-medium" viewBox="0 0 16 16"><path d="m12.9975267 12.999368c.5467123 0 1.0024733.4478567 1.0024733 1.000316 0 .5563109-.4488226 1.000316-1.0024733 1.000316h-9.99505341c-.54671233 0-1.00247329-.4478567-1.00247329-1.000316 0-.5563109.44882258-1.000316 1.00247329-1.000316zm-4.9975267-11.999368c.55228475 0 1 .44497754 1 .99589209v6.80214418l2.4816273-2.48241149c.3928222-.39294628 1.0219732-.4006883 1.4030652-.01947579.3911302.39125371.3914806 1.02525073-.0001404 1.41699553l-4.17620792 4.17752758c-.39120769.3913313-1.02508144.3917306-1.41671995-.0000316l-4.17639421-4.17771394c-.39122513-.39134876-.39767006-1.01940351-.01657797-1.40061601.39113012-.39125372 1.02337105-.3931606 1.41951349.00310701l2.48183446 2.48261871v-6.80214418c0-.55001601.44386482-.99589209 1-.99589209z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-info-filled-medium" viewBox="0 0 18 18"><path d="m9 0c4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9zm0 7h-1.5l-.11662113.00672773c-.49733868.05776511-.88337887.48043643-.88337887.99327227 0 .47338693.32893365.86994729.77070917.97358929l.1126697.01968298.11662113.00672773h.5v3h-.5l-.11662113.0067277c-.42082504.0488782-.76196299.3590206-.85696816.7639815l-.01968298.1126697-.00672773.1166211.00672773.1166211c.04887817.4208251.35902055.761963.76398144.8569682l.1126697.019683.11662113.0067277h3l.1166211-.0067277c.4973387-.0577651.8833789-.4804365.8833789-.9932723 0-.4733869-.3289337-.8699473-.7707092-.9735893l-.1126697-.019683-.1166211-.0067277h-.5v-4l-.00672773-.11662113c-.04887817-.42082504-.35902055-.76196299-.76398144-.85696816l-.1126697-.01968298zm0-3.25c-.69035594 0-1.25.55964406-1.25 1.25s.55964406 1.25 1.25 1.25 1.25-.55964406 1.25-1.25-.55964406-1.25-1.25-1.25z" fill-rule="evenodd"/></symbol><symbol id="icon-eds-i-mail-medium" viewBox="0 0 24 24"><path d="m19.462 0c1.413 0 2.538 1.184 2.538 2.619v12.762c0 1.435-1.125 2.619-2.538 2.619h-16.924c-1.413 0-2.538-1.184-2.538-2.619v-12.762c0-1.435 1.125-2.619 2.538-2.619zm.538 5.158-7.378 6.258a2.549 2.549 0 0 1 -3.253-.008l-7.369-6.248v10.222c0 .353.253.619.538.619h16.924c.285 0 .538-.266.538-.619zm-.538-3.158h-16.924c-.264 0-.5.228-.534.542l8.65 7.334c.2.165.492.165.684.007l8.656-7.342-.001-.025c-.044-.3-.274-.516-.531-.516z"/></symbol><symbol id="icon-eds-i-menu-medium" viewBox="0 0 24 24"><path d="M21 4a1 1 0 0 1 0 2H3a1 1 0 1 1 0-2h18Zm-4 7a1 1 0 0 1 0 2H3a1 1 0 0 1 0-2h14Zm4 7a1 1 0 0 1 0 2H3a1 1 0 0 1 0-2h18Z"/></symbol><symbol id="icon-eds-i-search-medium" viewBox="0 0 24 24"><path d="M11 1c5.523 0 10 4.477 10 10 0 2.4-.846 4.604-2.256 6.328l3.963 3.965a1 1 0 0 1-1.414 1.414l-3.965-3.963A9.959 9.959 0 0 1 11 21C5.477 21 1 16.523 1 11S5.477 1 11 1Zm0 2a8 8 0 1 0 0 16 8 8 0 0 0 0-16Z"/></symbol><symbol id="icon-eds-i-user-single-medium" viewBox="0 0 24 24"><path d="M12 1a5 5 0 1 1 0 10 5 5 0 0 1 0-10Zm0 2a3 3 0 1 0 0 6 3 3 0 0 0 0-6Zm-.406 9.008a8.965 8.965 0 0 1 6.596 2.494A9.161 9.161 0 0 1 21 21.025V22a1 1 0 0 1-1 1H4a1 1 0 0 1-1-1v-.985c.05-4.825 3.815-8.777 8.594-9.007Zm.39 1.992-.299.006c-3.63.175-6.518 3.127-6.678 6.775L5 21h13.998l-.009-.268a7.157 7.157 0 0 0-1.97-4.573l-.214-.213A6.967 6.967 0 0 0 11.984 14Z"/></symbol><symbol id="icon-eds-i-warning-filled-medium" viewBox="0 0 18 18"><path d="m9 11.75c.69035594 0 1.25.5596441 1.25 1.25s-.55964406 1.25-1.25 1.25-1.25-.5596441-1.25-1.25.55964406-1.25 1.25-1.25zm.41320045-7.75c.55228475 0 1.00000005.44771525 1.00000005 1l-.0034543.08304548-.3333333 4c-.043191.51829212-.47645714.91695452-.99654578.91695452h-.15973424c-.52008864 0-.95335475-.3986624-.99654576-.91695452l-.33333333-4c-.04586475-.55037702.36312325-1.03372649.91350028-1.07959124l.04148683-.00259031zm-.41320045 14c-4.97056275 0-9-4.0294373-9-9 0-4.97056275 4.02943725-9 9-9 4.9705627 0 9 4.02943725 9 9 0 4.9705627-4.0294373 9-9 9z" fill-rule="evenodd"/></symbol><symbol id="icon-expand-image" viewBox="0 0 18 18"><path d="m7.49754099 11.9178212c.38955542-.3895554.38761957-1.0207846-.00290473-1.4113089-.39324695-.3932469-1.02238878-.3918247-1.41130883-.0029047l-4.10273549 4.1027355.00055454-3.5103985c.00008852-.5603185-.44832171-1.006032-1.00155062-1.0059446-.53903074.0000852-.97857527.4487442-.97866268 1.0021075l-.00093318 5.9072465c-.00008751.553948.44841131 1.001882 1.00174994 1.0017946l5.906983-.0009331c.5539233-.0000875 1.00197907-.4486389 1.00206646-1.0018679.00008515-.5390307-.45026621-.9784332-1.00588841-.9783454l-3.51010549.0005545zm3.00571741-5.83449376c-.3895554.38955541-.3876196 1.02078454.0029047 1.41130883.393247.39324696 1.0223888.39182478 1.4113089.00290473l4.1027355-4.10273549-.0005546 3.5103985c-.0000885.56031852.4483217 1.006032 1.0015506 1.00594461.5390308-.00008516.9785753-.44874418.9786627-1.00210749l.0009332-5.9072465c.0000875-.553948-.4484113-1.00188204-1.0017499-1.00179463l-5.906983.00093313c-.5539233.00008751-1.0019791.44863892-1.0020665 1.00186784-.0000852.53903074.4502662.97843325 1.0058884.97834547l3.5101055-.00055449z" fill-rule="evenodd"/></symbol><symbol id="icon-github" viewBox="0 0 100 100"><path fill-rule="evenodd" clip-rule="evenodd" d="M48.854 0C21.839 0 0 22 0 49.217c0 21.756 13.993 40.172 33.405 46.69 2.427.49 3.316-1.059 3.316-2.362 0-1.141-.08-5.052-.08-9.127-13.59 2.934-16.42-5.867-16.42-5.867-2.184-5.704-5.42-7.17-5.42-7.17-4.448-3.015.324-3.015.324-3.015 4.934.326 7.523 5.052 7.523 5.052 4.367 7.496 11.404 5.378 14.235 4.074.404-3.178 1.699-5.378 3.074-6.6-10.839-1.141-22.243-5.378-22.243-24.283 0-5.378 1.94-9.778 5.014-13.2-.485-1.222-2.184-6.275.486-13.038 0 0 4.125-1.304 13.426 5.052a46.97 46.97 0 0 1 12.214-1.63c4.125 0 8.33.571 12.213 1.63 9.302-6.356 13.427-5.052 13.427-5.052 2.67 6.763.97 11.816.485 13.038 3.155 3.422 5.015 7.822 5.015 13.2 0 18.905-11.404 23.06-22.324 24.283 1.78 1.548 3.316 4.481 3.316 9.126 0 6.6-.08 11.897-.08 13.526 0 1.304.89 2.853 3.316 2.364 19.412-6.52 33.405-24.935 33.405-46.691C97.707 22 75.788 0 48.854 0z"/></symbol><symbol id="icon-springer-arrow-left"><path d="M15 7a1 1 0 000-2H3.385l2.482-2.482a.994.994 0 00.02-1.403 1.001 1.001 0 00-1.417 0L.294 5.292a1.001 1.001 0 000 1.416l4.176 4.177a.991.991 0 001.4.016 1 1 0 00-.003-1.42L3.385 7H15z"/></symbol><symbol id="icon-springer-arrow-right"><path d="M1 7a1 1 0 010-2h11.615l-2.482-2.482a.994.994 0 01-.02-1.403 1.001 1.001 0 011.417 0l4.176 4.177a1.001 1.001 0 010 1.416l-4.176 4.177a.991.991 0 01-1.4.016 1 1 0 01.003-1.42L12.615 7H1z"/></symbol><symbol id="icon-submit-open" viewBox="0 0 16 17"><path d="M12 0c1.10457 0 2 .895431 2 2v5c0 .276142-.223858.5-.5.5S13 7.276142 13 7V2c0-.512836-.38604-.935507-.883379-.993272L12 1H6v3c0 1.10457-.89543 2-2 2H1v8c0 .512836.38604.935507.883379.993272L2 15h6.5c.276142 0 .5.223858.5.5s-.223858.5-.5.5H2c-1.104569 0-2-.89543-2-2V5.828427c0-.530433.210714-1.039141.585786-1.414213L4.414214.585786C4.789286.210714 5.297994 0 5.828427 0H12Zm3.41 11.14c.250899.250899.250274.659726 0 .91-.242954.242954-.649606.245216-.9-.01l-1.863671-1.900337.001043 5.869492c0 .356992-.289839.637138-.647372.637138-.347077 0-.647371-.285256-.647371-.637138l-.001043-5.869492L9.5 12.04c-.253166.258042-.649726.260274-.9.01-.242954-.242954-.252269-.657731 0-.91l2.942184-2.951303c.250908-.250909.66127-.252277.91353-.000017L15.41 11.14ZM5 1.413 1.413 5H4c.552285 0 1-.447715 1-1V1.413ZM11 3c.276142 0 .5.223858.5.5s-.223858.5-.5.5H7.5c-.276142 0-.5-.223858-.5-.5s.223858-.5.5-.5H11Zm0 2c.276142 0 .5.223858.5.5s-.223858.5-.5.5H7.5c-.276142 0-.5-.223858-.5-.5s.223858-.5.5-.5H11Z" fill-rule="nonzero"/></symbol></svg> </div> </body> </html>