C. elegans screen identifies autophagy genes specific to multicellular organisms.
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.
Tian
Ye
Y
National Institute of Biological Sciences, Beijing 102206, P.R. China.
Li
Zhipeng
Z
Hu
Wanqiu
W
Ren
Haiyan
H
Tian
E
E
Zhao
Yu
Y
Lu
Qun
Q
Huang
Xinxin
X
Yang
Peiguo
P
Li
Xin
X
Wang
Xiaochen
X
Kovács
Attila L
AL
Yu
Li
L
Zhang
Hong
H
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
D029742:Caenorhabditis elegans Proteins