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

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

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.

Afiliação

Kumar S; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Jain A; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
Farzam F; Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Jia J; Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM.
Gu Y; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Choi SW; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
Mudd MH; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Claude-Taupin A; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
Wester MJ; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Lidke KA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
Rusten TE; Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Deretic V; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.

J Cell Biol ; 217(3): 997-1013, 2018 03 05.

Article em En | MEDLINE | ID: mdl-29420192

RESUMO

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.

Assuntos

Autofagossomos/metabolismo; Família da Proteína 8 Relacionada à Autofagia/metabolismo; Proteínas de Ligação ao GTP/metabolismo; Proteínas Qa-SNARE/metabolismo; Família da Proteína 8 Relacionada à Autofagia/genética; Proteínas de Ligação ao GTP/genética; Células HEK293; Infecções por HIV/genética; Infecções por HIV/metabolismo; HIV-1/genética; HIV-1/metabolismo; Células HeLa; Humanos; Transporte Proteico/genética; Proteínas Qa-SNARE/genética; Células THP-1; Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética; Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Ligação ao GTP / Proteínas Qa-SNARE / Autofagossomos / Família da Proteína 8 Relacionada à Autofagia Limite: Humans Idioma: En Revista: J Cell Biol Ano de publicação: 2018 Tipo de documento: Article

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