Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai, Japan.
Biochem Biophys Res Commun. 2010 Jul 30;398(3):426-32. doi: 10.1016/j.bbrc.2010.06.092. Epub 2010 Jul 1.
p120-Catenin is known to play important roles in cell-cell adhesion stability by binding to cadherin and morphological changes of cells by regulating small RhoGTPase activities. Although the expression and binding states of p120-catenin are thought to dynamically change due to morphological adaptation of endothelial cells (ECs) to fluid shear stress, these dynamics remain to be explored. In the present study, we examined the time course of changes in p120-catenin expression and its binding to vascular endothelial (VE)-cadherin in ECs exposed to shear stress. Human umbilical vein ECs began to change their morphologies at 3-6h, and became elongated and oriented to the direction of flow at 24h after exposure to a shear stress of 1.5Pa. Binding and co-localization of p120-catenin with VE-cadherin at the foci of cell-cell adhesions were retained in ECs during exposure to shear stress, indicating that VE-cadherin was stabilized in the plasma membrane. In contrast, cytoplasmic p120-catenin that was dissociated from VE-cadherin was transiently increased at 3-6h after the flow onset. These results suggest that the transient increase of cytoplasmic p120-catenin may stimulate RhoGTPase activities and act as a switch for the morphological changes in ECs in response to shear stress.
p120-连环蛋白通过与钙黏蛋白结合,在细胞间黏附稳定性中发挥重要作用,并通过调节小 RhoGTPase 活性来调节细胞的形态变化。尽管 p120-连环蛋白的表达和结合状态被认为由于内皮细胞(ECs)对流体切应力的形态适应而动态变化,但这些动态变化仍有待探索。在本研究中,我们研究了暴露于切应力下的 ECs 中 p120-连环蛋白表达及其与血管内皮(VE)-钙黏蛋白结合的变化过程。人脐静脉 ECs 在暴露于 1.5Pa 的切应力 3-6 小时后开始改变形态,在 24 小时后变得细长并朝向流动方向。在暴露于切应力期间,p120-连环蛋白与 VE-钙黏蛋白在细胞间黏附焦点的结合和共定位得以保留,表明 VE-钙黏蛋白在质膜中得到稳定。相比之下,与 VE-钙黏蛋白分离的细胞质 p120-连环蛋白在流动开始后 3-6 小时短暂增加。这些结果表明,细胞质 p120-连环蛋白的短暂增加可能刺激 RhoGTPase 活性,并作为 ECs 对切应力响应的形态变化的开关。