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Molecular control mechanism of the cadherin-mediated cell-cell adhesion

钙粘蛋白介导的细胞间粘附的分子控制机制

基本信息

批准号：
16570097
负责人：
OZAWA Masayuki
金额：
$ 2.37万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16570097/
关键词：
cadherin catenin traffic p120 cell surface transport Golgi body regulation 細胞質 v-Src チロシンリン酸化 Hakai ユビキチン化分解

项目摘要

The E-cadherin-catenin complex regulates calcium ion-dependent cell-cell adhesion and is localized to the basal-lateral membrane of polarized epithelial cells. Little is known about mechanisms of complex assembly or inrtracellular trafficking, or how these processes might ultimately regulate adhesion functions of the complex at the cell surface. Deletions of the region of the cytoplasmic domain of E-cadherin involved in beta-catenin-binding resulted in delivery of <10% of these proteins to cell surfaces. An E-cadherin construct uncoupled for beta-catenin-binding by amino acid substitutions in the region was also localized intracellularly. Thus, beta-catenin binding to the cytoplasmic domain of E-cadherin seemed to be required for the efficient transport to the cell surface. Contrary to this observation, >90% of E-cadherin lacking its entire cytoplasmic domain was detected on the surface of cells. To define the region of the E-cadherin cytoplasmic domain responsible for the intracellular accumulation of the beta-catenin-uncoupled E-cadherin constructs, we made a series of deletion constructs. Removal of the membrane-proximal region resulted in the cell surface expression of the constructs. Uncoupling p120-binding, however, did not change the distribution of the constructs.

E-钙粘蛋白-连环蛋白复合物调节钙离子依赖性细胞间粘附，并定位于极化上皮细胞的基底侧膜。关于复合物组装或细胞内运输的机制，或者这些过程如何最终调节细胞表面复合物的粘附功能，人们知之甚少。删除参与 β-连环蛋白结合的 E-钙粘蛋白胞质结构域区域会导致这些蛋白质的递送至细胞表面的比例小于 10%。通过该区域的氨基酸取代而解偶联用于 β-连环蛋白结合的 E-钙粘蛋白构建体也位于细胞内。因此，β-连环蛋白与 E-钙粘蛋白的胞质结构域结合似乎是有效转运至细胞表面所必需的。与此观察相反，在细胞表面检测到> 90% 缺乏整个细胞质结构域的 E-钙粘蛋白。为了定义负责β-连环蛋白解偶联的E-钙粘蛋白构建体的细胞内积累的E-钙粘蛋白胞质结构域的区域，我们制作了一系列缺失构建体。近膜区域的去除导致构建体在细胞表面表达。然而，解偶联 p120 结合并没有改变构建体的分布。