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

The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.
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DOI:
10.1111/tra.12204
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发表时间:
2014-11
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Colicelli J
Colicelli J
中科院分区:
其他
文献类型:
--
作者:
Balaji K;French CT;Miller JF;Colicelli J

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单核细胞增多性李斯特菌是一种食源性致病菌,它通过依赖宿主细胞RAB5 GTP酶激活的吞噬途径入侵肠道上皮细胞。然而,单核细胞增多性乳杆菌必须随后抑制RAB5,才能逃避溶酶体介导的破坏。单增李斯特氏菌进入上皮细胞和吞噬小体逃逸过程中,RAB5的上游调控因子知之甚少。在这里,我们确定RIN1,一个RAS效应器和RAB5导向的环境因子,是单核细胞增多性李斯特氏菌感染的宿主细胞因子。RIN1在单核细胞增多性李斯特菌感染后迅速激活,是肠道上皮细胞有效侵袭所必需的。RIN1介导的RAB5激活后来促进了吞噬小体与溶酶体的融合,促进了细菌从宿主细胞中的清除。这些结果表明,RIN1是一种宿主细胞调节因子,在单核细胞增多性李斯特菌感染的早期和晚期发挥平衡功能,最终有利于病原体的清除。
Listeria monocytogenes is a food-borne pathogenic bacterium that invades intestinal epithelial cells through a phagocytic pathway that relies on activation of host cell RAB5 GTPases. L. 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 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.
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