Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact
Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact
复制标题
DOI：
10.1091/mbc.e03-08-0582
复制
发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Noritake, J;Fukata, M;Kaibuchi, K
小的鸟苷三磷酸酶Rac 1被E-钙粘蛋白介导的细胞-细胞粘附激活，并且是肌动蛋白丝、E-钙粘蛋白和β-连环蛋白在细胞-细胞接触位点积累所必需的。然而，Rac 1的激活和作用模式仍有待澄清。我们在这里发现，IQGAP 1，肌动蛋白结合蛋白和Rac 1的效应，抑制小干扰RNA明显减少肌动蛋白丝，E-钙粘蛋白，β-连环蛋白的积累在网站的细胞接触在Madin-Darby犬肾11上皮细胞的条件下，Rac 1的敲低减少他们。Rac 1的敲除并不影响这些连接组件在表达Rac 1/Cdc 42结合缺陷的组成型活性IQGAP 1突变体的细胞中的定位。Rac 1或IQGAP 1的敲除加速了12-O-十四酰佛波醇-13-乙酸酯诱导的细胞-细胞解离。在IQGAP 1敲低的细胞中，由E-钙粘蛋白介导的细胞-细胞粘附维持的基础Rac 1活性受到抑制，而在过表达IQGAP 1的细胞中Rac 1活性增加。总之，这些结果表明Rac 1通过作用于IQGAP 1增强肌动蛋白丝、E-钙粘蛋白和β-连环蛋白的积累，并表明存在一个正反馈回路，该回路由“E-钙粘蛋白介导的细胞间粘附--> Rac 1激活--> IQGAP 1形成肌动蛋白网络-->增加E-钙粘蛋白介导的细胞间粘附”组成。"
The small guanosine triphosphatase Rac1 is activated by E-cadherin-mediated cell-cell adhesion and is required for the accumulation of actin filaments, E-cadherin, and beta-catenin at sites of cell-cell contact. However, the modes of activation and action of Rac1 remain to be clarified. We here found that suppression of IQGAP1, an actin-binding protein and an effector of Rac1, by small interfering RNA apparently reduced the accumulation of actin filaments, E-cadherin, and beta-catenin at sites of cell-cell contact in Madin-Darby canine kidney 11 epithelial cells under the conditions in which knockdown of Rac1 reduced them. Knockdown of Rac1 did not affect the localization of these junctional components in cells expressing a constitutively active IQGAP1 mutant defective in Rac1/Cdc42 binding. Knockdown of either Rac1 or IQGAP1 accelerated the 12-O-tetradecanoylphorbol-13-acetate-induced cell-cell dissociation. The basal Rac1 activity, which was maintained by E-cadherin-mediated cell-cell adhesion, was inhibited in the IQGAP1-knocked down cells, whereas the Rac1 activity was increased in the cells overexpressing IQGAP1. Together, these results indicate that Rac1 enhances the accumulation of actin filaments, E-cadherin, and beta-catenin by acting on IQGAP1 and suggest that there exists a positive feedback loop comprised of "E-cadherin-mediated cell-cell adhesion-->Rac1 activation-->actin-meshwork formation by IQGAP1-->increasing E-cadherin-mediated cell-cell adhesion."