Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas.
Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas.
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DOI：
10.1091/mbc.e06-06-0492
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发表时间：
2006-11
影响因子：
3.3
通讯作者：
Jing-Hua Shi;J. Casanova
中科院分区：
文献类型：
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作者：
Jing-Hua Shi;J. Casanova
鼠伤寒沙门氏菌通过将一系列效应蛋白注射到宿主细胞中诱导附着细菌的吞噬摄取来定殖肠上皮。然而，这些效应物靶向的宿主分子仍然不清楚。在这里，我们证明了S。鼠伤寒沙门氏菌在细菌附着位点诱导粘着斑样复合物的形成，粘着斑激酶（FAK）和支架蛋白p130 Cas都是沙门氏菌摄取所需的。沙门氏菌进入FAK（-/-）细胞的能力显著受损，并且可以通过野生型FAK的表达恢复到对照水平。令人惊讶的是，细菌内化的重建既不需要FAK的激酶结构域，也不需要c-Src的活化，但需要FAK与Cas相互作用的C-末端PXXP基序。Cas（-/-）细胞的感染也受损，并且侵袭性的重建需要中心Cas YXXP重复结构域。过表达FAK可抑制Cas（-/-）细胞的侵袭缺陷，表明FAK和Cas在沙门氏菌侵袭调控中的功能联系。总之，这些发现揭示了一个新的作用，粘着斑蛋白在宿主细胞的沙门氏菌的入侵。
Salmonella typhimurium colonizes the intestinal epithelium by injecting an array of effector proteins into host cells that induces phagocytic uptake of attached bacteria. However, the host molecules targeted by these effectors remain poorly defined. Here, we demonstrate that S. typhimurium induces formation of focal adhesion-like complexes at sites of bacterial attachment and that both focal adhesion kinase (FAK) and the scaffolding protein p130Cas are required for Salmonella uptake. Entry of Salmonella into FAK(-/-) cells is dramatically impaired and can be restored to control levels by expression of wild-type FAK. Surprisingly, reconstitution of bacterial internalization requires neither the kinase domain of FAK nor activation of c-Src, but does require a C-terminal PXXP motif through which FAK interacts with Cas. Infection of Cas(-/-) cells is also impaired, and reconstitution of invasiveness requires the central Cas YXXP repeat domain. The invasion defect in Cas(-/-) cells can be suppressed by overexpression of FAK, suggesting a functional link between FAK and Cas in the regulation of Salmonella invasion. Together, these findings reveal a novel role for focal adhesion proteins in the invasion of host cells by Salmonella.