title: The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes.
abstract: PtdIns(3)P plays critical roles in the autophagy pathway. However, little is known about how PtdIns(3)P effectors act with autophagy proteins in autophagosome formation. Here we identified an essential autophagy gene in C. elegans, epg-6, which encodes a WD40 repeat-containing protein with PtdIns(3)P-binding activity. EPG-6 directly interacts with ATG-2. epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures. Another WD40 repeat PtdIns(3)P effector, ATG-18, plays a distinct role in autophagosome formation. We also established the hierarchical relationship of autophagy genes in degradation of protein aggregates and revealed that the UNC-51/Atg1 complex, EPG-8/Atg14, and binding of lipidated LGG-1 to protein aggregates are required for omegasome formation. Our study demonstrates that autophagic PtdIns(3)P effectors play distinct roles in autophagosome formation and also provides a framework for understanding the concerted action of autophagy genes in protein aggregate degradation.
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Peiguo
authors.initials: P
authors.lastname: Yang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Long
authors.initials: L
authors.lastname: Lin
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 / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004721:Endoplasmic Reticulum / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007668:Kidney / Q000166:cytology; D008247:Lysosomes / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D008840:Microfilament Proteins; C534958:SEPA-1 protein, C elegans; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins