Phosphorylation of Syntaxin 17 by TBK1 Controls Autophagy Initiation.

Kumar, Suresh; Gu, Yuexi; Abudu, Yakubu Princely; Bruun, Jack-Ansgar; Jain, Ashish; Farzam, Farzin; Mudd, Michal; Anonsen, Jan Haug; Rusten, Tor Erik; Kasof, Gary; Ktistakis, Nicholas; Lidke, Keith A; Johansen, Terje; Deretic, Vojo

Kumar, Suresh; Gu, Yuexi; Abudu, Yakubu Princely; Bruun, Jack-Ansgar; Jain, Ashish; Farzam, Farzin; Mudd, Michal; Anonsen, Jan Haug; Rusten, Tor Erik; Kasof, Gary; Ktistakis, Nicholas; Lidke, Keith A; Johansen, Terje; Deretic, Vojo.

Afiliación

Kumar S; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Gu Y; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Abudu YP; Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, The Arctic University of Norway, Tromsø 9037, Norway.
Bruun JA; Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, The Arctic University of Norway, Tromsø 9037, Norway.
Jain A; Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo 0379, Norway.
Farzam F; Departments of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Mudd M; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Anonsen JH; Department of Biosciences IBV Mass Spectrometry and Proteomics Unit, University of Oslo, Oslo 0371, Norway.
Rusten TE; Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo 0379, Norway.
Kasof G; Cell Signaling Technology, Danvers, MA 01923, USA.
Ktistakis N; Signalling Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
Lidke KA; Departments of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Johansen T; Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, The Arctic University of Norway, Tromsø 9037, Norway.
Deretic V; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic addr

Dev Cell ; 49(1): 130-144.e6, 2019 04 08.

Article en En | MEDLINE | ID: mdl-30827897

RESUMEN

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.

Asunto(s)

Autofagia/genética; Complejos Multiproteicos/genética; Proteínas Serina-Treonina Quinasas/genética; Proteínas Qa-SNARE/genética; Proteínas Adaptadoras Transductoras de Señales/genética; Autofagosomas/metabolismo; Proteínas Relacionadas con la Autofagia/genética; Técnicas de Inactivación de Genes; Aparato de Golgi/genética; Aparato de Golgi/metabolismo; Células HEK293; Células HeLa; Humanos; Lisosomas/metabolismo; Fusión de Membrana/genética; Complejos Multiproteicos/metabolismo; Mutación/genética; Fosforilación; Proteínas Tirosina Quinasas/genética; Transducción de Señal/genética

Palabras clave

TBK1; ULK1; autophagy; pre-autophagosomal structure

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Proteínas Serina-Treonina Quinasas / Complejos Multiproteicos / Proteínas Qa-SNARE Límite: Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

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