Salmonella acquires lysosome-associated membrane protein 1 (LAMP1) on phagosomes from Golgi via SipC protein-mediated recruitment of host Syntaxin6

J Biol Chem. 2012 Feb 17;287(8):5574-87. doi: 10.1074/jbc.M111.286120. Epub 2011 Dec 21.

Abstract

Several intracellular pathogens have developed diverse strategies to avoid targeting to lysosomes. However, they universally recruit lysosome-associated membrane protein 1 (LAMP1); the mechanism of LAMP1 recruitment remains unclear. Here, we report that a Salmonella effector protein, SipC, specifically binds with host Syntaxin6 through its C terminus and thereby recruits Syntaxin6 and other accessory molecules like VAMP2, Rab6, and Rab8 on Salmonella-containing phagosomes (SCP) and acquires LAMP1 by fusing with LAMP1-containing Golgi-derived vesicles. In contrast, sipC knock-out:SCP (sipC(-):SCP) or sipC(M398K):SCP fails to obtain significant amounts of Syntaxin6 and is unable to acquire LAMP1. Moreover, phagosomes containing respective knock-out Salmonella like sipA(-), sipB(-), sipD(-), sopB(-), or sopE(-) recruit LAMP1, demonstrating the specificity of SipC in this process. In addition, depletion of Syntaxin6 by shRNA in macrophages significantly inhibits LAMP1 recruitment on SCP. Additionally, survival of sipC(-):Salmonella in mice is found to be significantly inhibited in comparison with WT:Salmonella. Our results reveal a novel mechanism showing how Salmonella acquires LAMP1 through a SipC-Syntaxin6-mediated interaction probably to stabilize their niche in macrophages and also suggest that similar modalities might be used by other intracellular pathogens to recruit LAMP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / microbiology
  • Intracellular Space / metabolism
  • Intracellular Space / microbiology
  • Lysosomal-Associated Membrane Protein 1 / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Mutation
  • Phagosomes / metabolism*
  • Phagosomes / microbiology*
  • Protein Transport
  • Qa-SNARE Proteins / metabolism*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / physiology
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • Lysosomal-Associated Membrane Protein 1
  • Qa-SNARE Proteins
  • Salmonella invasion protein C