Wibbe Nicolina, Steinbacher Tim, Tellkamp Frederik, Beckmann Niklas, Brinkmann Frauke, Stecher Manuel, Gerke Volker, Niessen Carien M, Ebnet Klaus
Institute-Associated Research Group "Cell Adhesion and Cell Polarity", Institute of Medical Biochemistry, Zentrum für Molekularbiologie der Entzündung, University Münster, Münster, Germany.
Department Cell Biology of the Skin, University Hospital of Cologne, University of Cologne, Cologne, Germany.
Front Cell Dev Biol. 2024 Jul 17;12:1279723. doi: 10.3389/fcell.2024.1279723. eCollection 2024.
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.
极化上皮细胞的细胞间接触形成是一个多步骤过程，涉及Rho家族小GTP酶的协同活动。与Rho GTP酶的核心作用一致，在连接成熟的各个阶段，已在细胞间连接处鉴定出许多Rho鸟嘌呤核苷酸交换因子（GEF）和Rho GTP酶激活蛋白（GAP）。与RhoGEF和RhoGAP不同，Rho GDP解离抑制剂（GDI）在细胞间接触形成过程中的作用了解甚少。在这里，我们分析了RhoGDI家族成员RhoGDI1/ARHGDIA在极化上皮细胞细胞间接触形成过程中的作用。RhoGDI1的缺失会延迟线性细胞间连接的发育以及形成屏障的紧密连接的形成。此外，RhoGDI1的缺失会损害细胞响应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募集到细胞间接触部位。我们的数据表明RhoGDI1参与了涉及细胞间连接动态重组的各种过程。
