Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells.
Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells.
复制标题
皮尔塔克蛋白和CRK在志贺氏菌入侵上皮细胞期间触发肌动蛋白聚合。
DOI：
10.1083/jcb.200402073
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发表时间：
2004-07-19
影响因子：
7.8
通讯作者：
Van Nhieu, Guy Tran
中科院分区：
文献类型：
--
作者：
Bougneres, Laurence;Girardin, Stephane E;Weed, Scott A;Karginov, Andrei V;Olivo-Marin, Jean-Christophe;Parsons, J Thomas;Sansonetti, Philippe J;Van Nhieu, Guy Tran
志贺氏菌是细菌性痢疾的病原体，在一个涉及Src酪氨酸激酶信号转导的过程中入侵上皮细胞。Cortactin是一种普遍存在的肌动蛋白结合蛋白，存在于肌动蛋白的动态组装结构中，是志贺氏菌入侵过程中被磷酸化的主要蛋白酪氨酸。在这里，我们报告说，RNA干扰沉默皮质蛋白的表达，就像在表达激酶非活性的Src的细胞中抑制Src一样，干扰肌动蛋白聚合，而肌动蛋白聚合是形成吞噬细菌的细胞延伸所必需的。志贺氏菌的侵袭以酪氨酸磷酸化依赖的方式诱导质膜上皮质蛋白的募集。野生型Cortactin或接头蛋白Crk的过表达有利于志贺氏菌的摄取，Arp2/3结合缺陷的Cortactin衍生物或Src同源2结构域Crk突变体干扰细菌诱导的肌动蛋白焦点的形成。研究表明，Crk直接与酪氨酸磷酸化的皮质肌动蛋白相互作用，并调节依赖于皮质肌动蛋白的肌动蛋白聚合，这是志贺氏菌摄取所必需的。这些结果表明，Crk-Cortactin复合体在酪氨酸激酶信号转导下游的肌动蛋白聚合中起着重要作用。
Shigella, the causative agent of bacillary dysentery, invades epithelial cells in a process involving Src tyrosine kinase signaling. Cortactin, a ubiquitous actin-binding protein present in structures of dynamic actin assembly, is the major protein tyrosine phosphorylated during Shigella invasion. Here, we report that RNA interference silencing of cortactin expression, as does Src inhibition in cells expressing kinase-inactive Src, interferes with actin polymerization required for the formation of cellular extensions engulfing the bacteria. Shigella invasion induced the recruitment of cortactin at plasma membranes in a tyrosine phosphorylation–dependent manner. Overexpression of wild-type forms of cortactin or the adaptor protein Crk favored Shigella uptake, and Arp2/3 binding–deficient cortactin derivatives or an Src homology 2 domain Crk mutant interfered with bacterial-induced actin foci formation. Crk was shown to directly interact with tyrosine-phosphorylated cortactin and to condition cortactin-dependent actin polymerization required for Shigella uptake. These results point at a major role for a Crk–cortactin complex in actin polymerization downstream of tyrosine kinase signaling.