Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy

Nature Communications
Chenyao WangZhixue Liu

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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Citations

Aug 25, 2020·Journal of Biochemical and Molecular Toxicology·Fatemeh YarmohammadiGholamreza Karimi
Sep 15, 2020·Autophagy·Xiaoyu TianJianguo Chen
Jun 19, 2019·Autophagy·Douglas S GrunwaldDo-Hyung Kim
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Methods Mentioned

BETA
pull down
pull-downs
transfections
pull-down
protein IP
transmission electron microscopy
immunoprecipitation
co-IP
confocal microscopy
transfection

Software Mentioned

GPS
DPS
PSW
MaxQuant

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