Stx17 通过 IRGM 和哺乳动物 Atg8 蛋白招募到自噬体的机制。

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

机构信息

Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.

Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.

出版信息

J Cell Biol. 2018 Mar 5;217(3):997-1013. doi: 10.1083/jcb.201708039. Epub 2018 Feb 2.

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.

自噬是一种保守的真核生物过程，在哺乳动物细胞中具有代谢、免疫和一般的体内平衡功能。哺乳动物的自噬体与溶酶体融合是一个 SNARE 驱动的过程，其中包括突触融合蛋白 17（Stx17）。Stx17 如何转位到自噬体尚不清楚。在这项研究中，我们表明，Stx17 在人类细胞中招募到自噬体的机制需要小分子鸟苷三磷酸酶 IRGM。Stx17 直接与 IRGM 相互作用，并且有效的 Stx17 招募到自噬体需要 IRGM。IRGM 和 Stx17 都直接与哺乳动物 Atg8 蛋白相互作用，从而被引导到自噬体。我们还表明，Stx17 在抵御感染性病原体方面具有重要作用，并且 HIV 毒力因子 Nef 靶向 Stx17-IRGM 相互作用。