The WD40 Repeat PtdIns(3)P-Binding Protein EPG-6 Regulates Progression of Omegasomes to Autophagosomes
The WD40 Repeat PtdIns(3)P-Binding Protein EPG-6 Regulates Progression of Omegasomes to Autophagosomes
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DOI：
10.1016/j.devcel.2011.06.024
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发表时间：
2011-08-16
影响因子：
11.8
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Lu, Qun;Yang, Peiguo;Zhang, Hong
PtdIns（3）P在自噬途径中起关键作用。然而，关于PtdIns（3）P效应器如何在自噬体形成中与自噬蛋白作用的知之甚少。在这里，我们确定了一个重要的自噬基因在C。elegans，epg-6，其编码具有PtdIns（3）P-结合活性的含WD 40重复序列的蛋白。EPG-6直接与ATG-2相互作用。EPG-6和ATG-2调节ω体向自噬体的进展，它们的功能丧失导致扩大的早期自噬结构的积累。另一种WD 40重复PtdIns（3）P效应物ATG-18在自噬体形成中起独特作用。我们还建立了自噬基因在蛋白质聚集体降解中的层次关系，并揭示了UNC 51/Atg 1复合物，EPG-8/Atg 14和过时的LGG-1与蛋白质聚集体的结合是omegasome形成所必需的。我们的研究表明自噬PtdIns（3）P效应子在自噬体的形成中起着独特的作用，也为理解自噬基因在蛋白质聚集体降解中的协同作用提供了一个框架。
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 UNC51/Atg1 complex, EPG-8/Atg14, and binding of lipi-dated 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.