title: A role for Atg8-PE deconjugation in autophagosome biogenesis.
abstract: Formation of the autophagosome is likely the most complex step of macroautophagy, and indeed it is the morphological and functional hallmark of this process; accordingly, it is critical to understand the corresponding molecular mechanism. Atg8 is the only known autophagy-related (Atg) protein required for autophagosome formation that remains associated with the completed sequestering vesicle. Approximately one-fourth of all of the characterized Atg proteins that participate in autophagosome biogenesis affect Atg8, regulating its conjugation to phosphatidylethanolamine (PE), localization to the phagophore assembly site and/or subsequent deconjugation. An unanswered question in the field regards the physiological role of the deconjugation of Atg8-PE. Using an Atg8 mutant that bypasses the initial Atg4-dependent processing, we demonstrate that Atg8 deconjugation is an important step required to facilitate multiple events during macroautophagy. The inability to deconjugate Atg8-PE results in the mislocalization of this protein to the vacuolar membrane. We also show that the deconjugation of Atg8-PE is required for efficient autophagosome biogenesis, the assembly of Atg9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated Atg components.
authors.affiliation: Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Usha
authors.initials: U
authors.lastname: Nair
authors.forename: Wei-Lien
authors.initials: WL
authors.lastname: Yen
authors.forename: Muriel
authors.initials: M
authors.lastname: Mari
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xie
authors.forename: Misuzu
authors.initials: M
authors.lastname: Baba
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D002451:Cell Compartmentation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C483858:phosphatidylethanolamine