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

National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
Developmental Cell (Impact Factor: 9.71). 08/2011; 21(2):343-57. DOI: 10.1016/j.devcel.2011.06.024
Source: PubMed


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.

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    • "Although it is not possible to conclude that Atg101 is not required for Atg8a recruitment to ref(2)P aggregates solely based on RNAi experiments, this seems to be a possibility, which is also supported by data from mutant worms. Interestingly, of the core Atg genes, Atg2 has also been shown to be dispensable for Atg8a recruitment to the phagophore assembly site and protein aggregates in worm, fly, and mammalian cells [19, 24, 36, 37]. To exclude the possibility that these Atg8a dots might represent autophagosomes, we carried out electron microscopy. "
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