Department of Surgery, University of Chicago, Chicago, IL 60637, USA.
Mol Cell Biol. 2010 Apr;30(8):1971-83. doi: 10.1128/MCB.01247-09. Epub 2010 Feb 12.
It is crucial for organ homeostasis that epithelia have effective mechanisms to restrict motility and cell proliferation in order to maintain tissue architecture. On the other hand, epithelial cells need to rapidly and transiently acquire a more mesenchymal phenotype, with high levels of cell motility and proliferation, in order to repair epithelia upon injury. Cross talk between cell-cell and cell-matrix signaling is crucial for regulating these transitions. The Pak1-betaPIX-GIT complex is an effector complex downstream of the small GTPase Rac1. We previously showed that translocation of this complex from cell-matrix to cell-cell adhesion sites was required for the establishment of contact inhibition of proliferation. In this study, we provide evidence that this translocation depends on cadherin function. Cadherins do not recruit the complex by direct interaction. Rather, we found that inhibition of the normal function of cadherin or Pak1 leads to defects in focal adhesion turnover and to increased signaling by phosphatidylinositol 3-kinase. We propose that cadherins are involved in regulation of contact inhibition by controlling the function of the Pak1-betaPIX-GIT complex at focal contacts.
上皮组织具有限制运动和增殖的有效机制对于维持组织结构至关重要。另一方面，上皮细胞需要迅速而短暂地获得更具间充质表型的特征，具有高细胞运动性和增殖能力，以便在受伤后修复上皮组织。细胞-细胞和细胞-基质信号的串扰对于调节这些转变至关重要。Pak1-βPIX-GIT 复合物是小 GTPase Rac1 的下游效应复合物。我们之前表明，该复合物从细胞-基质向细胞-细胞黏附位点的易位对于建立增殖接触抑制是必需的。在这项研究中，我们提供了证据表明这种易位依赖于钙黏蛋白的功能。钙黏蛋白不会通过直接相互作用招募复合物。相反，我们发现抑制钙黏蛋白或 Pak1 的正常功能会导致焦点粘连的周转率缺陷，并导致磷酸肌醇 3-激酶信号的增加。我们提出，钙黏蛋白通过控制 Pak1-βPIX-GIT 复合物在焦点接触处的功能参与接触抑制的调节。
