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 |