ULK1 phosphorylates Sec23A and mediates autophagy-induced inhibition of ER-to-Golgi traffic

Wenjia Gan, Caiyun Zhang, Ka Yu Siu, Ayano Satoh, Julian A. Tanner, Sidney Yu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed. Results: In this study, we identified Sec23A, a component of the COPII vesicle coat, as a target of ULK1 phosphorylation. Elevated autophagy, induced by amino acid starvation, rapamycin, or overexpression of ULK1 caused aggregation of the ERES, a region of the ER dedicated for the budding of COPII vesicles. Transport of cargo proteins was also inhibited under these conditions and was retained at the ERES. ULK1 phosphorylation of Sec23A reduced the interaction between Sec23A and Sec31A. We identified serine 207, serine 312 and threonine 405 on Sec23A as ULK1 phosphorylation sites. Among these residues, serine 207, when changed to phospho-deficient and phospho-mimicking mutants, most faithfully recapitulated the above-mentioned effects of ULK1 phospho-regulation. Conclusion: These findings identify Sec23A as a new target of ULK1 and uncover a mechanism of coordinating intracellular protein transport and autophagy.

Original languageEnglish
Article number22
JournalBMC Cell Biology
Volume18
Issue number1
DOIs
Publication statusPublished - May 10 2017

Fingerprint

Autophagy
Serine
Phosphorylation
Serotonin Plasma Membrane Transport Proteins
Proteins
Secretory Pathway
Protein Transport
Sirolimus
Threonine
Starvation
Carrier Proteins
Phosphotransferases
Amino Acids
Food

Keywords

  • Autophagy
  • COPII
  • ER exit sites
  • Sec23
  • ULK1

ASJC Scopus subject areas

  • Cell Biology

Cite this

ULK1 phosphorylates Sec23A and mediates autophagy-induced inhibition of ER-to-Golgi traffic. / Gan, Wenjia; Zhang, Caiyun; Siu, Ka Yu; Satoh, Ayano; Tanner, Julian A.; Yu, Sidney.

In: BMC Cell Biology, Vol. 18, No. 1, 22, 10.05.2017.

Research output: Contribution to journalArticle

Gan, Wenjia ; Zhang, Caiyun ; Siu, Ka Yu ; Satoh, Ayano ; Tanner, Julian A. ; Yu, Sidney. / ULK1 phosphorylates Sec23A and mediates autophagy-induced inhibition of ER-to-Golgi traffic. In: BMC Cell Biology. 2017 ; Vol. 18, No. 1.
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