The RAB5-GEF Function of RIN1 Regulates Multiple Steps During Listeria monocytogenes Infection

Kavitha Balaji, Christopher T. French, Jeff F. Miller, John Colicelli

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1206-1218
Number of pages13
JournalTraffic
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Keywords

  • Listeria monocytogenes
  • MET
  • Phagosome
  • RAB5
  • RIN1

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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