| Literature DB >> 26237647 |
Na Mi1, Yang Chen1, Shuai Wang2, Mengran Chen2, Mingkun Zhao1, Guang Yang1, Meisheng Ma1, Qian Su3, Sai Luo1, Jingwen Shi1, Jia Xu1, Qiang Guo4, Ning Gao4, Yujie Sun3, Zhucheng Chen2, Li Yu1.
Abstract
A fundamental question regarding autophagosome formation is how the shape of the double-membrane autophagosomal vesicle is generated. Here we show that in mammalian cells assembly of an actin scaffold inside the isolation membrane (the autophagosomal precursor) is essential for autophagosomal membrane shaping. Actin filaments are depolymerized shortly after starvation and actin is assembled into a network within the isolation membrane. When formation of actin puncta is disrupted by an actin polymerization inhibitor or by knocking down the actin-capping protein CapZβ, isolation membranes and omegasomes collapse into mixed-membrane bundles. Formation of actin puncta is PtdIns(3)P dependent, and inhibition of PtdIns(3)P formation by treating cells with the PI(3)K inhibitor 3-MA, or by knocking down Beclin-1, abolishes the formation of actin puncta. Binding of CapZ to PtdIns(3)P, which is enriched in omegasomes, stimulates actin polymerization. Our findings illuminate the mechanism underlying autophagosomal membrane shaping and provide key insights into how autophagosomes are formed.Entities:
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Year: 2015 PMID： 26237647 DOI： 10.1038/ncb3215
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824