| Literature DB >> 30827897 |
Suresh Kumar1, Yuexi Gu1, Yakubu Princely Abudu2, Jack-Ansgar Bruun2, Ashish Jain3, Farzin Farzam4, Michal Mudd1, Jan Haug Anonsen5, Tor Erik Rusten3, Gary Kasof6, Nicholas Ktistakis7, Keith A Lidke4, Terje Johansen2, Vojo Deretic8.
Abstract
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. Published by Elsevier Inc.Entities:
Keywords: TBK1; ULK1; autophagy; pre-autophagosomal structure
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Year: 2019 PMID： 30827897 PMCID： PMC6907693 DOI： 10.1016/j.devcel.2019.01.027
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270