Crosstalk between cell-cell adhesion and signaling

粘附连接（AJs）和紧密连接（TJs）是一种连接复合物，不仅在上皮细胞的粘附和极化中起关键作用，而且在细胞运动和增殖的调节中起关键作用。E-Cadherin和connectin是AJs上主要的细胞粘附分子（CAMs），而claudin是TJs上主要的CAM。我们已经证明，钙粘蛋白为基础的细胞-细胞粘附在MDCK细胞中不会形成，其中膜联蛋白II （Ca^<2+>-和磷脂结合蛋白）被敲除。我们还发现，在膜联蛋白ii敲低的细胞中形成了TJs和连接蛋白基细胞-细胞粘附。在膜联蛋白ii敲低的MDCK细胞中，TJs的形成需要以连接蛋白为基础的细胞-细胞粘附和afadin（一种连接蛋白和肌动蛋白-丝结合蛋白）。此外，它还需要激活Cdc42和Rac小G蛋白，并随后重组iqgap1依赖的肌动蛋白骨架，这是由连接蛋白为基础的细胞-细胞粘附诱导的。这些结果表明，TJs的形成需要连接素为基础的细胞间粘附和afadin，而不是钙粘蛋白为基础的细胞间粘附，连接素的信号传导和随后的肌动蛋白细胞骨架的重组也是TJs形成所必需的。

Adherens junctions (AJs) and tight junctions (TJs) comprise a junctional complex which plays key roles not only in cell adhesion and polarization but also in regulation of cell movement and proliferation in epithelial cells. E-Cadherin and nectin are major cell-cell adhesion molecules (CAMs) at AJs, whereas claudin is a major CAM at TJs. We have shown that the cadherin-based cell-cell adhesion is not formed in MDCK cells in which annexin II, a Ca^<2+>- and phospholipid-binding protein, is knocked down. We have also found that TJs and the nectin-based cell-cell adhesion were formed in annexin II-knockdown cells. The formation of TJs in annexin II-knockdown MDCK cells required the nectin-based cell-cell adhesion and afadin, a nectin- and actin-filament-binding protein. In addition, it required the activation of Cdc42 and Rac small G proteins and subsequent reorganization of the IQGAP1-dependent actin cytoskeleton which were induced by the nectin-based cell-cell adhesion. These results indicate that the nectin-based cell-cell adhesion and afadin, but not the cadherin-based cell-cell adhesion, are necessary for the formation of TJs and that the signaling by nectin and the subsequent reorganization of the actin cytoskeleton are also necessary for the formation of TJs.