SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell.
SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell.
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DOI：
10.3389/fcimb.2017.00257
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发表时间：
2017
影响因子：
5.7
通讯作者：
Teasdale RD
中科院分区：
文献类型：
--
作者：
Liebl D;Qi X;Zhe Y;Barnett TC;Teasdale RD
鼠伤寒沙门氏菌（Salmonella enterica serovar Typhimurium，S.鼠伤寒沙门氏菌）通过经由III型分泌系统递送穿过宿主细胞膜的毒力蛋白的作用诱导巨胞饮。我们表明，对接后，在质膜S。鼠伤寒沙门氏菌触发胞质SNX 18（一种SH 3-PX-BAR结构域分选连接蛋白）快速募集至细菌诱导的膜皱褶和新生的含沙门氏菌的空泡。SNX 18的招募需要沙门氏菌效应子SopB的肌醇磷酸酶活性和SNX 18 PX结构域内的完整磷酸肌醇结合位点，但独立于Rho-GTPases Rac 1和Cdc 42激活而发生。SNX 18通过在依赖于SNX 18的SH 3结构域的过程中充当募集发动蛋白-2和N-WASP的支架来促进SCV从质膜形成。细菌摄取的定量显示，SNX 18的过表达增加了细菌的内化，而在过表达磷酸肌醇结合突变体R303 Q、Δ SH 3突变体的细胞中以及在内源性SNX 18水平被敲低的细胞中检测到了降低。这项研究确定SNX 18为SopB的新靶点，并提出了S.鼠伤寒杆菌通过在入侵部位局部操纵磷酸肌醇组成来参与宿主因子，以协调内化过程。
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation. SNX18 promotes formation of the SCV from the plasma membrane by acting as a scaffold to recruit Dynamin-2 and N-WASP in a process dependent on the SH3 domain of SNX18. Quantification of bacteria uptake revealed that overexpression of SNX18 increased bacteria internalization, whereas a decrease was detected in cells overexpressing the phosphoinositide-binding mutant R303Q, the ΔSH3 mutant, and in cells where endogenous levels of SNX18 were knocked-down. This study identifies SNX18 as a novel target of SopB and suggests a mechanism where S. Typhimurium engages host factors via local manipulation of phosphoinositide composition at the site of invasion to orchestrate the internalization process.