Mechanism of Stx17 recruitment to autophagosomes via IRGM and mammalian Atg8 proteins

Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNARE-driven process that includes syntaxin 17 (Stx17). How Stx17 translocates to autophagosomes is unknown. In this study, we s...

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Detalles Bibliográficos
Autores principales: Kumar, Suresh, Jain, Ashish, Farzam, Farzin, Jia, Jingyue, Gu, Yuexi, Choi, Seong Won, Mudd, Michal H., Claude-Taupin, Aurore, Wester, Michael J., Lidke, Keith A., Rusten, Tor-Erik, Deretic, Vojo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839791/
https://www.ncbi.nlm.nih.gov/pubmed/29420192
http://dx.doi.org/10.1083/jcb.201708039
Descripción
Sumario:Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNARE-driven process that includes syntaxin 17 (Stx17). How Stx17 translocates to autophagosomes is unknown. In this study, we show that the mechanism of Stx17 recruitment to autophagosomes in human cells entails the small guanosine triphosphatase IRGM. Stx17 directly interacts with IRGM, and efficient Stx17 recruitment to autophagosomes requires IRGM. Both IRGM and Stx17 directly interact with mammalian Atg8 proteins, thus being guided to autophagosomes. We also show that Stx17 is significant in defense against infectious agents and that Stx17–IRGM interaction is targeted by an HIV virulence factor Nef.

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