CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane

Author:

Mi, Na  Chen, Yang  Wang, Shuai  Chen, Mengran  Zhao, Mingkun  Yang, Guang  Ma, Meisheng  Su, Qian  Luo, Sai  Shi, Jingwen  Xu, Jia  Guo, Qiang  Gao, Ning  Sun, Yujie  Chen, Zhucheng  Yu, Li  

Journal:

NATURE CELL BIOLOGY

Issue Date:

2015

Abstract(summary):

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 CapZ beta, 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.

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