Developmental Cell
Volume 49, Issue 1, 8 April 2019, Pages 130-144.e6
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Article
Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation

https://doi.org/10.1016/j.devcel.2019.01.027Get rights and content
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Highlights

  • Syntaxin 17 functions during autophagy initiation and bulk cargo sequestration

  • TBK1 phosphorylates syntaxin 17 at Ser202 (Stx17pS202)

  • Stx17pS202 translocates from Golgi to pre-autophagosomal structure upon starvation

  • Stx17pS202 controls formation of FIP200-ATG13 pre-autophagosomal structures

Summary

Syntaxin 17 (Stx17) has been implicated in autophagosome-lysosome fusion. Here, we report that Stx17 functions in assembly of protein complexes during autophagy initiation. Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202. During autophagy induction, Stx17pS202 transfers from the Golgi, where its steady-state pools localize, to the ATG13+FIP200+ mPAS. Stx17pS202 was in complexes with ATG13 and FIP200, whereas its non-phosphorylatable mutant Stx17S202A was not. Stx17 or TBK1 knockouts blocked ATG13 and FIP200 puncta formation. Stx17 or TBK1 knockouts reduced the formation of ATG13 protein complexes with FIP200 and ULK1. Endogenous Stx17pS202 colocalized with LC3B following induction of autophagy. Stx17 knockout diminished LC3 response and reduced sequestration of the prototypical bulk autophagy cargo lactate dehydrogenase. We conclude that Stx17 is a TBK1 substrate and that together they orchestrate assembly of mPAS.

Keywords

autophagy
TBK1
ULK1
pre-autophagosomal structure

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