Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts
Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts
复制标题
DOI：
10.1091/mbc.e05-04-0330
复制
发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Yap, AS
中科院分区：
文献类型：
--
作者：
Shewan, AM;Maddugoda, M;Yap, AS
经典的钙粘蛋白在细胞-细胞接触处积累，作为对生产性粘附连接的特征性反应。这种钙粘蛋白的局部积累是一个发育调节的过程，支持细胞粘附和细胞-细胞粘附。然而，负责钙粘蛋白积累的分子效应仍然不完全清楚。我们现在报告，肌球蛋白2是关键的细胞集中E-钙粘蛋白在细胞与细胞接触。肌球蛋白2存在于基于钙粘蛋白的细胞-细胞接触处，其募集需要E-钙粘蛋白活性。事实上，肌球蛋白2的募集和激活都受到E-钙粘蛋白同型连接的刺激。通过blebbistatin或ML-7抑制肌球蛋白2活性，可迅速损害细胞在粘附接触处浓缩E-钙粘蛋白的能力，同时降低基于钙粘蛋白的细胞粘附性。钙粘蛋白的总表面表达不受影响，这表明肌球蛋白2主要调节钙粘蛋白在细胞表面的区域分布。肌球蛋白2与钙粘蛋白接触的募集及其激活需要Rho激酶;此外，抑制Rho激酶信号传导有效地表型化肌球蛋白2抑制的作用。我们提出肌球蛋白2是Rho-Rho激酶信号传导的关键效应子，该信号传导通过确定细胞响应于嗜同性连接而在接触处浓缩钙粘蛋白的能力来调节细胞-细胞粘附。
Classical cadherins accumulate at cell-cell contacts as a characteristic response to productive adhesive ligation. Such local accumulation of cadherins is a developmentally regulated process that supports cell adhesiveness and cell-cell cohesion. Yet the molecular effectors responsible for cadherin accumulation remain incompletely understood. We now report that Myosin 2 is critical for cells to concentrate E-cadherin at cell-cell contacts. Myosin 2 is found at cadherin-based cell-cell contacts and its recruitment requires E-cadherin activity. Indeed, both Myosin 2 recruitment and its activation were stimulated by E-cadherin homophilic ligation alone. Inhibition of Myosin 2 activity by blebbistatin or ML-7 rapidly impaired the ability of cells to concentrate E-cadherin at adhesive contacts, accompanied by decreased cadherin-based cell adhesiveness. The total surface expression of cadherins was unaffected, suggesting that Myosin 2 principally regulates the regional distribution of cadherins at the cell surface. The recruitment of Myosin 2 to cadherin contacts, and its activation, required Rho kinase; furthermore, inhibition of Rho kinase signaling effectively phenocopied the effects of Myosin 2 inhibition. We propose that Myosin 2 is a key effector of Rho-Rho kinase signaling that regulates cell-cell adhesion by determining the ability of cells to concentrate cadherins at contacts in response to homophilic ligation.