title: The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.
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.
authors.affiliation: Department of Biological Chemistry, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Balaji
authors.forename: Christopher T
authors.initials: CT
authors.lastname: French
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Miller
authors.forename: John
authors.initials: J
authors.lastname: Colicelli
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008247:Lysosomes; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D051381:Rats; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C092117:RIN1 protein, human; D020663:ras Guanine Nucleotide Exchange Factors; D020696:rab5 GTP-Binding Proteins
keywords: Listeria monocytogenes; MET; RAB5; RIN1; phagosome
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