MYO6 is targeted by Salmonella virulence effectors to trigger PI3-kinase signaling and pathogen invasion into host cells
MYO6 is targeted by Salmonella virulence effectors to trigger PI3-kinase signaling and pathogen invasion into host cells
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DOI：
10.1073/pnas.1616418114
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发表时间：
2017-04-11
影响因子：
11.1
通讯作者：
Koronakis, Vassilis
中科院分区：
文献类型：
--
作者：
Brooks, Andrew B. E.;Humphreys, Daniel;Koronakis, Vassilis
为了建立感染，沙门氏菌注射毒力效应物，劫持宿主肌动蛋白细胞骨架和磷酸肌苷信号来驱动病原体入侵。效应器如何重编程细胞骨架网络仍不清楚。通过重组沙门氏菌效应物SopE的活性，我们在无细胞提取物中重现了Rho gtpase在模型磷脂膜双层上驱动的肌动蛋白聚合，并鉴定了Rho募集的细胞骨架蛋白网络。网络组分的敲低揭示了肌凝蛋白VI （MYO6）在沙门氏菌入侵中的关键作用。SopE触发MYO6定位于侵袭灶，SopE介导的PAK激活将MYO6招募到富含肌动蛋白的膜上。我们发现毒力效应物SopB需要MYO6来调节PIP3和PI(3) P磷酸肌苷的定位和Akt的激活。SopE和SopB以MYO6为靶点，协调侵袭灶处磷酸肌苷的产生，促进细胞骨架适配蛋白的募集，介导病原体的摄取。
To establish infections, Salmonella injects virulence effectors that hijack the host actin cytoskeleton and phosphoinositide signaling to drive pathogen invasion. How effectors reprogram the cytoskeleton network remains unclear. By reconstituting the activities of the Salmonella effector SopE, we recapitulated Rho GTPase-driven actin polymerization at model phospholipid membrane bilayers in cell-free extracts and identified the network of Rho-recruited cytoskeleton proteins. Knockdown of network components revealed a key role for myosin VI (MYO6) in Salmonella invasion. SopE triggered MYO6 localization to invasion foci, and SopE-mediated activation of PAK recruited MYO6 to actin-rich membranes. We show that the virulence effector SopB requires MYO6 to regulate the localization of PIP3 and PI(3) P phosphoinositides and Akt activation. SopE and SopB target MYO6 to coordinate phosphoinositide production at invasion foci, facilitating the recruitment of cytoskeleton adaptor proteins to mediate pathogen uptake.