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整合素通过调节Src 激酶的激活和肌动球蛋白收缩来刺激 E-钙黏蛋白介导的细胞间黏附。

Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src-kinase activation and actomyosin contractility.

机构信息

UMR144 CNRS-Institut Curie, 75248 Paris Cedex 05, France.

出版信息

J Cell Sci. 2010 Mar 1;123(Pt 5):712-22. doi: 10.1242/jcs.047878. Epub 2010 Feb 9.

DOI:10.1242/jcs.047878
PMID:20144995
Abstract

Cadherins and integrins are major adhesion molecules regulating cell-cell and cell-matrix interactions. In vitro and in vivo studies have demonstrated the existence of crosstalk between integrins and cadherins in cell adhesion and motility. We used a dual pipette assay to measure the force required to separate E-cadherin-producing cell doublets and to investigate the role of integrin in regulating the strength of intercellular adhesion. A greater force was required to separate cell doublets bound to fibronectin or vitronectin-coated beads than for doublets bound to polylysine-coated beads. This effect depended on cell spreading and the duration of stimulation. Cells expressing type II cadherin-7 also responded to fibronectin stimulation to produce a higher intercellular adhesion. Establishment of cadherin-mediated adhesion needed ROCK, MLCK and myosin ATPase II activity. The regulation of intercellular adhesion strength by integrin stimulation required activation of Src family kinases, ROCK and actomyosin contractility. These findings highlight the importance and mechanisms of molecular crosstalk between cadherins and integrins in the control of cell plasticity during histogenesis and morphogenesis.

摘要

钙黏蛋白和整合素是调节细胞-细胞和细胞-基质相互作用的主要黏附分子。体外和体内研究表明,整合素和钙黏蛋白在细胞黏附和迁移中存在串扰。我们使用双管测定法来测量分离产生 E-钙黏蛋白的细胞二联体所需的力,并研究整合素在调节细胞间黏附强度中的作用。与结合多聚赖氨酸包被珠的二联体相比,结合纤维连接蛋白或玻连蛋白包被珠的二联体需要更大的力才能分离。这种效应取决于细胞的铺展和刺激的持续时间。表达 II 型钙黏蛋白-7 的细胞也对纤维连接蛋白刺激作出反应,产生更高的细胞间黏附。钙黏蛋白介导的黏附的建立需要 ROCK、MLCK 和肌球蛋白 ATP 酶 II 活性。整合素刺激对细胞间黏附强度的调节需要激活Src 家族激酶、ROCK 和肌动球蛋白收缩性。这些发现强调了钙黏蛋白和整合素之间分子串扰在组织发生和形态发生过程中控制细胞可塑性的重要性和机制。

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