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

被引:121
作者
Kumar, Suresh [1 ,2 ]
Jain, Ashish [3 ,4 ]
Farzam, Farzin [5 ]
Jia, Jingyue [1 ,2 ]
Gu, Yuexi [1 ,2 ]
Choi, Seong Won [1 ,2 ]
Mudd, Michal H. [1 ,2 ]
Claude-Taupin, Aurore [1 ,2 ]
Wester, Michael J. [6 ]
Lidke, Keith A. [5 ]
Rusten, Tor-Erik [3 ,4 ]
Deretic, Vojo [1 ,2 ]
机构
[1] Univ New Mexico, Hlth Sci Ctr, Autophagy Inflammat & Metab Ctr Biomed Res Excell, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Dept Mol Genet & Microbiol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[3] Univ Oslo, Ctr Canc Biomed, Dept Mol Cell Biol, Oslo, Norway
[4] Norwegian Radium Hosp, Inst Canc Res, Oslo, Norway
[5] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA
[6] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA
基金
美国国家卫生研究院;
关键词
SNARE SYNTAXIN 17; SELECTIVE AUTOPHAGY; LYSOSOME FUSION; MEMBRANE-FUSION; HOPS COMPLEX; MYCOBACTERIUM-TUBERCULOSIS; MITOCHONDRIAL DIVISION; TETHERING COMPLEXES; ENDOCYTIC PATHWAY; CONTACT SITES;
D O I
10.1083/jcb.201708039
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autophagy is a conserved eukaryotic process with metabolic, immune, and general homeostatic functions in mammalian cells. Mammalian autophagosomes fuse with lysosomes in a SNA RE-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.
引用
收藏
页码:997 / 1013
页数:17
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