Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1
Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1
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DOI：
10.1038/sj.emboj.7600359
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发表时间：
2004-09-01
期刊：
影响因子：
11.4
通讯作者：
Abe, A
中科院分区：
文献类型：
--
作者：
Matsuzawa, T;Kuwae, A;Abe, A
致病性大肠杆菌通过III型分泌系统将效应子的子集递送到宿主细胞中，并且这一步骤是疾病进展所必需的。在这里，我们表明，III型效应器，EspG及其同系物Orf 3，触发肌动蛋白应力纤维的形成和破坏的微管网络下粘附细菌。这两种效应器被证明具有与微管蛋白相互作用的能力，并在体外刺激微管不稳定。最近的一项研究表明，微管结合GEF-H1，RhoA特异性鸟嘌呤核苷酸交换因子，通过微管去稳定化转化为其活性形式，这一系列事件导致RhoA刺激。事实上，EspG和Orf 3诱导的应力纤维的形成被抑制的GEF-H1和RhoA，但不Rac 1和Cdc 42的显性阴性形式的表达，并通过治疗与ROCK抑制剂。这些结果表明EspG/Orf 3对微管网络的影响通过GEF-H1活性触发RhoA-ROCK信号通路的激活。该报告首次揭示了病原体可以利用宿主因子GEF-H1。
Enteropathogenic Escherichia coli delivers a subset of effectors into host cells via a type III secretion system, and this step is required for the progression of disease. Here, we show that the type III effectors, EspG and its homolog Orf3, trigger actin stress fiber formation and the destruction of the microtubule networks beneath adherent bacteria. Both effectors were shown to possess the ability to interact with tubulins, and to stimulate microtubule destabilization in vitro. A recent study showed that microtubule-bound GEF-H1, a RhoA-specific guanine nucleotide exchange factor, was converted to its active form by microtubule destabilization, and this sequence of events resulted in RhoA stimulation. Indeed, EspG- and Orf3-induced stress fiber formation was inhibited by the expression of dominant-negative forms of GEF-H1 and RhoA, but not of Rac1 and Cdc42, and by treatment with a ROCK inhibitor. These results indicate that the impact of EspG/ Orf3 on microtubule networks triggers the activation of the RhoA-ROCK signaling pathway via GEF-H1 activity. This report reveals for the first time that a pathogen can exploit the host factor GEF-H1.