The WD40 Repeat PtdIns(3)P-Binding Protein EPG-6 Regulates Progression of Omegasomes to Autophagosomes

Qun Lu, Peiguo Yang, Xinxin Huang, Wanqiu Hu, Bin Guo, Fan Wu, Long Lin, Attila L. Kovács, Li Yu, Hong Zhang

Research output: Contribution to journalArticle

117 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)343-357
Number of pages15
JournalDevelopmental Cell
Volume21
Issue number2
DOIs
Publication statusPublished - Aug 16 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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