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dc.contributor.authorKumar, Suresh
dc.contributor.authorGu, Yuexi
dc.contributor.authorAbudu, Yakubu Princely
dc.contributor.authorBruun, Jack-Ansgar
dc.contributor.authorJain, Ashish
dc.contributor.authorFarzam, Farzin
dc.contributor.authorMudd, Michal H.
dc.contributor.authorAnonsen, Jan Haug
dc.contributor.authorRusten, Tor Erik
dc.contributor.authorKasof, Gary
dc.contributor.authorKtistakis, Nicholas
dc.contributor.authorLidke, Keith A
dc.contributor.authorJohansen, Terje
dc.contributor.authorDeretic, Vojo
dc.date.accessioned2020-03-10T08:45:54Z
dc.date.available2020-03-10T08:45:54Z
dc.date.issued2019-02-28
dc.description.abstractSyntaxin 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<sup>+</sup>FIP200<sup>+</sup> mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202. During autophagy induction, Stx17<sup>pS202</sup> transfers from the Golgi, where its steady-state pools localize, to the ATG13<sup>+</sup>FIP200<sup>+</sup> mPAS. Stx17<sup>pS202</sup> was in complexes with ATG13 and FIP200, whereas its non-phosphorylatable mutant Stx17<sup>S202A</sup> 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 Stx17<sup>pS202</sup> 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.en_US
dc.descriptionAccepted manuscript version, licensed <a href=http://creativecommons.org/licenses/by-nc-nd/4.0/> CC BY-NC-ND 4.0. </a>en_US
dc.identifier.citationKumar S, Gu Y, Abudu YP, Bruun JA, Jain Ashish Jain, Farzam F, Mudd MH, Anonsen JH, Rusten TE, Kasof, Ktistakis, Lidke KA, Johansen T, Deretic V. Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation. Developmental Cell. 2019;49(1):130-144.e6en_US
dc.identifier.cristinIDFRIDAID 1682218
dc.identifier.doi10.1016/j.devcel.2019.01.027
dc.identifier.issn1534-5807
dc.identifier.issn1878-1551
dc.identifier.urihttps://hdl.handle.net/10037/17690
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalDevelopmental Cell
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/249884/Norway/Autophagy-regulated Signalosomes in Cellular Stress and Disease Pathways//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holder© 2019 Elsevier B.V. All rights reserved.en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titlePhosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiationen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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