Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements
Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements
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DOI：
10.1371/journal.pbio.1000457
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发表时间：
2010-08-01
期刊：
影响因子：
9.8
通讯作者：
Meyer, Thomas F.
中科院分区：
文献类型：
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作者：
Boettcher, Jan Peter;Kirchner, Marieluise;Meyer, Thomas F.
某些细菌粘附素似乎促进病原体的细胞外生活方式，而不是其进入宿主细胞。然而，对这种病原体-宿主-细胞相互作用所引起的刺激知之甚少。在这里，我们报道了IV型毛菌（Tfp）产生淋病奈瑟菌（P(+)GC）诱导宿主细胞中Cav1 （Cav1）的立即募集，随后通过下游磷酸酪氨酸信号通路触发细胞骨架重排，阻止细菌内化。对酪氨酸磷酸化的Cav1的潜在相互作用伙伴进行了广泛而公正的分析，发现它与rho家族鸟嘌呤核苷酸交换因子Vav2直接相互作用。研究发现，Vav2及其底物小GTPase RhoA在cav1介导的细菌摄取预防中起直接作用。我们的研究结果已经扩展到肠致病性大肠杆菌，强调了产生tfp的细菌如何避免宿主细胞摄取。此外，我们的数据建立了Cav1磷酸化与病原体诱导的细胞骨架重组之间的机制联系，并促进了我们对Cav1蛋白功能的理解。
Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.