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

Author

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  • Chenyao Wang

    (University of Chinese Academy of Sciences
    Lerner Research Institute, Cleveland Clinic)

  • Huafei Wang

    (University of Chinese Academy of Sciences)

  • Deyi Zhang

    (University of Chinese Academy of Sciences)

  • Wenwen Luo

    (University of Chinese Academy of Sciences)

  • Ruilong Liu

    (University of Chinese Academy of Sciences)

  • Daqian Xu

    (The University of Texas MD Anderson Cancer Center)

  • Lei Diao

    (University of Chinese Academy of Sciences)

  • Lujian Liao

    (East China Normal University)

  • Zhixue Liu

    (University of Chinese Academy of Sciences
    Georgia State University)

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.

Suggested Citation

  • Chenyao Wang & Huafei Wang & Deyi Zhang & Wenwen Luo & Ruilong Liu & Daqian Xu & Lei Diao & Lujian Liao & Zhixue Liu, 2018. "Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05449-1
    DOI: 10.1038/s41467-018-05449-1
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