biostudies-literatureBalaji KNIDDK NIH HHSNCI NIH HHSPHS HHSNIGMS NIH HHS1206-18https://www.ebi.ac.uk/biostudies/studies/S-EPMC4282165biostudies-literatureUnknown15(11)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.Traffic (Copenhagen, Denmark)The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.PMC4282165U54 A1065359T32 GM007185R01 CA136699P30 DK041301CA136699Balaji KMiller JFColicelli JFrench CTfalseThe RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.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.2014-01-01T00:00:00Z2014 Nov2021-02-19T18:41:25Z2019-03-27T01:42:36ZS-EPMC42821652508207610.1111/tra.12204