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Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.3K

ULK1 phosphorylation of striatin activates protein phosphatase 2A and autophagy

Zehan Hu1, Devanarayanan Siva Sankar1, Bich Vu1

  • 1Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.

Cell Reports
|September 30, 2021
PubMed

Insights

The ULK1 kinase complex controls autophagy. This study reveals ULK1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Unc-51 like autophagy activating kinase 1 (ULK1) complex is essential for initiating canonical autophagy.
  • Understanding ULK1's regulation and broader roles in later autophagy stages is crucial.

Purpose of the Study:

  • To investigate ULK1's control mechanisms and its involvement in the complete autophagy process.
  • To identify direct ULK1 phosphorylation targets involved in autophagosome maturation and turnover.

Main Methods:

  • Comprehensive phosphoproteomic analysis combining in vivo and in vitro approaches.
  • Identification of direct ULK1 phosphorylation sites on autophagy-related proteins.

Main Results:

  • Numerous direct ULK1 phosphorylation targets critical for autophagosome maturation and turnover were identified.
  • A crosstalk between ULK1 and phosphatase complexes, specifically PP2A, was uncovered.
  • ULK1 was found to directly phosphorylate striatin, activating PP2A and creating a positive feedback loop for autophagy.

Conclusions:

  • ULK1 plays a significant role beyond autophagy initiation, influencing autophagosome maturation and turnover.
  • A coordinated interplay between ULK1 kinase and PP2A phosphatase activities tightly regulates protein degradation via autophagy.
  • This ULK1-phosphatase crosstalk provides a robust mechanism for controlling autophagy-dependent protein turnover.
Keywords:
PP2ASTRIPAKSTRNautophagyin vitro kinase assaykinasemass spectrometryphosphatasephosphoproteomicssignaling

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