PDF(Pubmed)
Abstract：
Cell-cell contact formation of polarized epithelial cells is a multi-step process that involves the co-ordinated activities of Rho family small GTPases. Consistent with the central role of Rho GTPases, a number of Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) have been identified at cell-cell junctions at various stages of junction maturation. As opposed to RhoGEFs and RhoGAPs, the role of Rho GDP dissociation inhibitors (GDIs) during cell-cell contact formation is poorly understood. Here, we have analyzed the role of RhoGDI1/ARHGDIA, a member of the RhoGDI family, during cell-cell contact formation of polarized epithelial cells. Depletion of RhoGDI1 delays the development of linear cell-cell junctions and the formation of barrier-forming tight junctions. In addition, RhoGDI1 depletion impairs the ability of cells to stop migration in response to cell collision and increases the migration velocity of collectively migrating cells. We also find that the cell adhesion receptor JAM-A promotes the recruitment of RhoGDI1 to cell-cell contacts. Our findings implicate RhoGDI1 in various processes involving the dynamic reorganization of cell-cell junctions.
摘要：
极化上皮细胞的细胞-细胞接触形成是一个多步骤的过程，涉及Rho家族小GTP酶的协调活性。与RhoGTPases的核心作用一致，在连接成熟的各个阶段，已在细胞-细胞连接处鉴定出许多Rho鸟嘌呤核苷酸交换因子（GEF）和RhoGTP酶激活蛋白（GAP）。与RhoGEF和RhoGAP相反，RhoGDP解离抑制剂（GDI）在细胞-细胞接触形成过程中的作用知之甚少。这里,我们分析了RhoGDI1/ARHGDIA的作用，RhoGDI家族的一员,在极化上皮细胞的细胞-细胞接触形成过程中。RhoGDI1的耗尽延迟了线性细胞-细胞连接的发展和形成屏障的紧密连接的形成。此外,RhoGDI1耗尽会损害细胞响应于细胞碰撞而停止迁移的能力，并增加集体迁移细胞的迁移速度。我们还发现细胞粘附受体JAM-A促进RhoGDI1募集到细胞-细胞接触。我们的发现暗示RhoGDI1参与了涉及细胞-细胞连接动态重组的各种过程。
