Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery
Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery
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DOI：
10.1038/ncb1526
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发表时间：
2007-01-01
影响因子：
21.3
通讯作者：
Sasakawa, Chihiro
中科院分区：
文献类型：
--
作者：
Handa, Yutaka;Suzuki, Masato;Sasakawa, Chihiro
志贺氏菌使用一种特殊的机制来侵入上皮细胞，称为“进入的触发机制”（1-3），它允许上皮细胞同时捕获几种细菌。在接触时，志贺氏菌通过III型分泌系统将效应物递送到上皮细胞中（4-6）。在这里，我们表明，效应器之一，IpgB 1，具有关键作用，通过利用RhoG-ELMO-Dock 180途径刺激Rac 1活性产生膜皱褶。使用下拉分析，我们确定了吞噬和细胞运动（埃尔莫）蛋白作为IpgB 1的结合伴侣。IpgB 1与埃尔莫和Dock 180共定位于志贺菌引起的膜皱褶。志贺氏菌的侵袭性和IpgB 1诱导的皱褶在埃尔莫和Dock 180敲低的细胞中比野生型细胞少。当细胞表达IpgB 1-埃尔莫嵌合体时，ELMO-Dock 180与皱褶的膜结合得到促进，从而确定IpgB 1模拟RhoG在产生膜皱褶中的作用。综上所述，我们的研究结果表明，IpgB 1模仿是志贺氏菌入侵的关键。
Shigella use a special mechanism to invade epithelial cells called 'the trigger mechanism of entry'(1-3), which allows epithelial cells to trap several bacteria simultaneously. On contact, Shigella deliver effectors into epithelial cells through the type III secretion system(4-6). Here, we show that one of the effectors, IpgB1, has a pivotal role in producing membrane ruffles by exploiting the RhoG-ELMO-Dock180 pathway to stimulate Rac1 activity. Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. Shigella invasiveness and IpgB1-induced ruffles were less in ELMO- and Dock180-knockdown cells compared with wild-type cells. Membrane association of ELMO-Dock180 with ruffles were promoted when cells expressed an IpgB1-ELMO chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane ruffles. Taken together, our findings show that IpgB1 mimicry is the key to invasion by Shigella.