The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection

Traffic. 2014 Nov;15(11):1206-18. doi: 10.1111/tra.12204. Epub 2014 Sep 4.

Abstract

Listeria monocytogenes is a food-borne pathogenic bacterium that invades intestinal epithelial cells through a phagocytic pathway that relies on the activation of host cell RAB5 GTPases. Listeria monocytogenes must subsequently inhibit RAB5, however, in order to escape lysosome-mediated destruction. Relatively little is known about upstream RAB5 regulators during L. monocytogenes entry and phagosome escape processes in epithelial cells. Here we identify RIN1, a RAS effector and RAB5-directed guanine nucleotide exchange factor (GEF), as a host cell factor in L. monocytogenes infection. RIN1 is rapidly engaged following L. monocytogenes infection and is required for efficient invasion of intestinal epithelial cells. RIN1-mediated RAB5 activation later facilitates the fusion of phagosomes with lysosomes, promoting clearance of bacteria from the host cell. These results suggest that RIN1 is a host cell regulator that performs counterbalancing functions during early and late stages of L. monocytogenes infection, ultimately favoring pathogen clearance.

Keywords: Listeria monocytogenes; MET; RAB5; RIN1; phagosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Listeria monocytogenes / pathogenicity*
  • Lysosomes
  • Phagocytosis
  • Phagosomes / metabolism
  • Rats
  • rab5 GTP-Binding Proteins / metabolism*
  • ras Guanine Nucleotide Exchange Factors / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • RIN1 protein, human
  • ras Guanine Nucleotide Exchange Factors
  • rab5 GTP-Binding Proteins