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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Bibliographic Details
Published in:The Journal of cell biology 2018-03, Vol.217 (3), p.997-1013
Main Authors: 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
Format: Article
Language:English
Subjects:
Autophagosomes - metabolism
Autophagy
Autophagy-Related Protein 8 Family - genetics
Autophagy-Related Protein 8 Family - metabolism
Cells
Cellular biology
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Guanosine
HEK293 Cells
HeLa Cells
HIV
HIV Infections - genetics
HIV Infections - metabolism
HIV-1 - genetics
HIV-1 - metabolism
Human immunodeficiency virus
Humans
Lysosomes
Mammalian cells
Mammals
nef Gene Products, Human Immunodeficiency Virus - genetics
nef Gene Products, Human Immunodeficiency Virus - metabolism
Nef protein
Phagocytosis
Phagosomes
Protein Transport - genetics
Proteins
Qa-SNARE Proteins - genetics
Qa-SNARE Proteins - metabolism
Recruitment
SNAP receptors
Syntaxin
THP-1 Cells
Triphosphatase
Virulence
Virulence factors
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201708039