Phosphorylation of ULK1 Affects Autophagosome Fusion and Links Chaperone-mediated Autophagy to Macroautophagy

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Aug 30

PMID 30154410

Citations 96

Authors

Chenyao Wang

Huafei Wang

Deyi Zhang

Wenwen Luo

Ruilong Liu

Daqian Xu

Lei Diao

Lujian Liao

Zhixue Liu

Affiliations

Soon will be listed here.

Abstract

The Unc-51 like autophagy activating kinase 1 (ULK1) complex plays a central role in the initiation stage of autophagy. However, the function of ULK1 in the late stage of autophagy is unknown. Here, we report that ULK1, a central kinase of the ULK1 complex involved in autophagy initiation, promotes autophagosome-lysosome fusion. PKCα phosphorylates ULK1 and prevents autolysosome formation. PKCα phosphorylation of ULK1 does not change its kinase activity; however, it decreases autophagosome-lysosome fusion by reducing the affinity of ULK1 for syntaxin 17 (STX17). Unphosphorylated ULK1 recruited STX17 and increased STX17's affinity towards synaptosomal-associated protein 29 (SNAP29). Additionally, phosphorylation of ULK1 enhances its interaction with heat shock cognate 70 kDa protein (HSC70) and increases its degradation through chaperone-mediated autophagy (CMA). Our study unearths a key mechanism underlying autolysosome formation, a process in which the kinase activity of PKCα plays an instrumental role, and reveals the significance of the mutual regulation of macroautophagy and CMA in maintaining the balance of autophagy.

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