Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src-kinase activation and actomyosin contractility
Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src-kinase activation and actomyosin contractility
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DOI：
10.1242/jcs.047878
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Dufour, Sylvie
中科院分区：
文献类型：
--
作者：
Martinez-Rico, Clara;Pincet, Frederic;Dufour, Sylvie
钙粘蛋白和整合素是调节细胞间和细胞与基质间相互作用的主要粘附分子。体外和体内研究表明，在细胞粘附和运动中整合素和钙粘素之间存在串扰。我们使用了双移液管测定分离E-钙粘蛋白产生细胞双联体所需的力，并研究整合素在调节细胞间粘附强度中的作用。需要更大的力来分离与纤连蛋白或玻连蛋白包被的珠结合的细胞双联体，而不是与聚赖氨酸包被的珠结合的双联体。这种效应依赖于细胞的扩散和刺激的持续时间。表达II型钙粘蛋白-7的细胞也响应于纤连蛋白刺激以产生更高的细胞间粘附。钙粘蛋白介导的粘附的建立需要ROCK、MLCK和肌球蛋白ATP酶II的活性。通过整联蛋白刺激调节细胞间粘附强度需要Src家族激酶、ROCK和肌动球蛋白收缩性的激活。这些发现突出了钙粘蛋白和整合素之间的分子串扰在组织发生和形态发生过程中的细胞可塑性控制的重要性和机制。
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.