IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42
IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42
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DOI：
10.1074/jbc.m702537200
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发表时间：
2007-10-12
影响因子：
4.8
通讯作者：
Sacks, David B.
中科院分区：
文献类型：
--
作者：
Brown, Matthew D.;Bry, Lynn;Sacks, David B.
为了感染宿主细胞，沙门氏菌利用复杂的系统来操纵肌动蛋白细胞骨架并促进细菌摄取。沙门氏菌注入宿主细胞的蛋白质激活Rho GTP酶Rac 1和Cdc 42，诱导肌动蛋白聚合。摄取后，一组不同的蛋白质使Rac 1和Cdc 42失活，使细胞骨架恢复正常。虽然沙门氏菌侵入宿主细胞的信号通路已开始被理解，但许多促成因素仍有待阐明。IQGAP 1是一种多结构域蛋白，影响许多细胞功能，包括调节Rac 1/Cdc 42信号传导和肌动蛋白聚合。在这里，我们报告了IQGAP 1调节沙门氏菌的入侵。通过与肌动蛋白的相互作用，IQGAP 1与Rac 1，Cdc 42和肌动蛋白共同定位在细菌摄取的位点，而感染促进IQGAP 1与Rac 1和Cdc 42的相互作用。IQGAP 1的敲除显着减少了沙门氏菌的入侵并消除了沙门氏菌对Cdc 42和Rac 1的激活。IQGAP 1的过表达显著增加沙门氏菌进入宿主细胞的能力，并需要与肌动蛋白和Cdc 42/Rac 1相互作用。总之，这些数据将IQGAP 1鉴定为沙门氏菌入侵的新型调节剂。
To infect host cells, Salmonella utilizes an intricate system to manipulate the actin cytoskeleton and promote bacterial uptake. Proteins injected into the host cell by Salmonella activate the Rho GTPases, Rac1 and Cdc42, to induce actin polymerization. Following uptake, a different set of proteins inactivates Rac1 and Cdc42, returning the cytoskeleton to normal. Although the signaling pathways allowing Salmonella to invade host cells are beginning to be understood, many of the contributing factors remain to be elucidated. IQGAP1 is a multidomain protein that influences numerous cellular functions, including modulation of Rac1/Cdc42 signaling and actin polymerization. Here, we report that IQGAP1 regulates Salmonella invasion. Through its interaction with actin, IQGAP1 co-localizes with Rac1, Cdc42, and actin at sites of bacterial uptake, whereas infection promotes the interaction of IQGAP1 with both Rac1 and Cdc42. Knockdown of IQGAP1 significantly reduces Salmonella invasion and abrogates activation of Cdc42 and Rac1 by Salmonella. Overexpression of IQGAP1 significantly increases the ability of Salmonella to enter host cells and required interaction with both actin and Cdc42/Rac1. Together, these data identify IQGAP1 as a novel regulator of Salmonella invasion.