title: C. elegans screen identifies autophagy genes specific to multicellular organisms.
abstract: The molecular understanding of autophagy has originated almost exclusively from yeast genetic studies. Little is known about essential autophagy components specific to higher eukaryotes. Here we perform genetic screens in C. elegans and identify four metazoan-specific autophagy genes, named epg-2, -3, -4, and -5. Genetic analysis reveals that epg-2, -3, -4, and -5 define discrete genetic steps of the autophagy pathway. epg-2 encodes a coiled-coil protein that functions in specific autophagic cargo recognition. Mammalian homologs of EPG-3/VMP1, EPG-4/EI24, and EPG-5/mEPG5 are essential for starvation-induced autophagy. VMP1 regulates autophagosome formation by controlling the duration of omegasomes. EI24 and mEPG5 are required for formation of degradative autolysosomes. This study establishes C. elegans as a multicellular genetic model to delineate the autophagy pathway and provides mechanistic insights into the metazoan-specific autophagic process.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Li
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Hu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ren
authors.forename: E
authors.initials: E
authors.lastname: Tian
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.forename: Peiguo
authors.initials: P
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D003594:Cytoplasmic Granules / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D010588:Phagosomes / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins