Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7
Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7
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DOI：
10.1016/j.celrep.2015.07.063
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发表时间：
2015-09-01
期刊：
影响因子：
8.8
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
D'Costa, Vanessa M.;Braun, Virginie;Brumell, John H.
不同性质的细胞内细菌病原体通过损害内吞货物运输到溶酶体进行降解而具有逃避宿主免疫的能力，这是一个知之甚少的过程。在这里，我们表明，肠道沙门氏菌3型分泌效应SopD2介导的结合宿主调节GTTRab7和抑制其核苷酸交换的过程。因此，这限制了Rab7与其动力蛋白和驱动蛋白结合效应物RILP和FYCO 1的相互作用，从而破坏了微管马达的宿主驱动调节。我们的研究确定了一种能够直接结合并从而调节Rab7活性的细菌效应子，以及一种内吞运输中断机制，这可能为了解其他细菌的发病机制提供帮助。此外，我们为Rab7功能的研究提供了一个强大的工具，也是一个潜在的治疗靶点。
Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.