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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autophagosomes / metabolism*
  • Autophagy-Related Protein 8 Family / genetics
  • Autophagy-Related Protein 8 Family / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • HEK293 Cells
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Protein Transport / genetics
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • THP-1 Cells
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Autophagy-Related Protein 8 Family
  • GABARAPL2 protein, human
  • Qa-SNARE Proteins
  • STX17 protein, human
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • GTP-Binding Proteins
  • IRGM protein, human