RRC ID 46156
著者 Lu Q, Yang P, Huang X, Hu W, Guo B, Wu F, Lin L, Kovács AL, Yu L, Zhang H.
タイトル The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes.
ジャーナル Dev Cell
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.
巻・号 21(2)
ページ 343-57
公開日 2011-8-16
DOI 10.1016/j.devcel.2011.06.024
PII S1534-5807(11)00258-9
PMID 21802374
MeSH Animals Autophagy / physiology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Cytoplasmic Granules / metabolism Embryo, Nonmammalian Endoplasmic Reticulum / physiology* Green Fluorescent Proteins / genetics Kidney / cytology Lysosomes / metabolism Microfilament Proteins / metabolism Mutation / genetics Phagosomes / metabolism* Protein Structure, Tertiary Rats Saccharomyces cerevisiae Proteins Transfection
IF 10.092
引用数 115
WOS 分野 DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm3425