title: The Atg17-Atg31-Atg29 Complex Coordinates with Atg11 to Recruit the Vam7 SNARE and Mediate Autophagosome-Vacuole Fusion.
abstract: Macroautophagy (hereafter autophagy) is an evolutionarily conserved process in which portions of the cytoplasm are engulfed, degraded, and subsequently recycled. The Atg17-Atg31-Atg29 complex translocates to the phagophore assembly site (PAS), where an autophagosome forms, at a very early stage of autophagy, playing a vital role in autophagy induction. Here, we identified a novel role of this complex in a late stage of autophagy where it coordinates with Atg11 to regulate autophagy-specific fusion with the vacuole. Atg17 and Atg11 interact with the vacuolar SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) Vam7 independently of each other. Several hydrophobic residues in helix 1 and helix 4 of Atg17 and the SNARE domain of Vam7 mediate the Atg17-Vam7 interaction. An F317D mutation of Atg17, which diminishes its interaction with Vam7 without affecting its interaction with Atg13 or Atg31, leads to a defect in the fusion of autophagosomes with the vacuole and decreased autophagy activity. These results provide the first demonstration that the Atg17-Atg31-Atg29 complex functions in both early and late stages of autophagy and also provide a mechanistic explanation for the coordination of autophagosome completion and fusion with the vacuole.
authors.affiliation: Life Sciences Institute and the Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Life Sciences Institute and the Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Mao
authors.affiliation: Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Angela Y H
authors.initials: AYH
authors.lastname: Yu
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Omairi-Nasser
authors.affiliation: Electron Microscopy Core Facility, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jotham
authors.initials: J
authors.lastname: Austin
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Glick
authors.affiliation: Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Calvin K
authors.initials: CK
authors.lastname: Yip
authors.affiliation: Life Sciences Institute and the Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: klionsky@umich.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: autophagy; lysosome; stress; vacuole; yeast