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

FULLTEXT
Published:
02.02.2018
|
Last Revised:
11.13.2018
PMID:
29420192
The Journal of cell biology
Journal Article
Authors:
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.
Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM.
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.
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.
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.
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.
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.
Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM.
Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM.
Department of Molecular Cell Biology, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM vderetic@salud.unm.edu.,Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.

Abstract

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.