Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes.

Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes.
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VCAM-1和ICAM-1与粘附白细胞的新型内皮对接结构中的动态相互作用。

DOI:
10.1083/jcb.200112126
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发表时间:
2002-06-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Sanchez-Madrid F
Sanchez-Madrid F
中科院分区:
其他
文献类型:
--
作者:
Barreiro O;Yanez-Mo M;Serrador JM;Montoya MC;Vicente-Manzanares M;Tejedor R;Furthmayr H;Sanchez-Madrid F

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Ezrin、radixin和moesin(ERM)通过将膜粘附受体连接到基于肌动蛋白的细胞骨架来调节皮质形态发生和细胞粘附。我们研究了膜突蛋白和埃兹蛋白与血管细胞粘附分子(VCAM)-1在白细胞粘附和跨内皮迁移(TEM)过程中的相互作用。VCAM-1在体外与膜突蛋白和埃兹蛋白直接相互作用,并且所有这些分子共定位于内皮的顶面。在活细胞中的这种相互作用的动态评估表明,VCAM-1和膜突蛋白参与淋巴母细胞粘附和内皮上的传播,而只有膜突蛋白参与TEM,遵循相同的分布模式作为ICAM-1。在静态或流动条件下的白细胞粘附过程中,VCAM-1、ICAM-1和活化的膜突蛋白和埃兹蛋白聚集在富含内皮肌动蛋白的对接结构中,该结构锚定并部分包围含有其他细胞骨架成分(如α-辅肌动蛋白、粘着斑蛋白和VASP)的白细胞。磷酸肌醇和Rho/p160 ROCK通路参与ERM蛋白的活化,参与锚定结构的产生和维持。这些结果提供了内皮对接结构的第一个表征,该结构在炎症期间白细胞与内皮的牢固粘附中起关键作用。
Ezrin, radixin, and moesin (ERM) regulate cortical morphogenesis and cell adhesion by connecting membrane adhesion receptors to the actin-based cytoskeleton. We have studied the interaction of moesin and ezrin with the vascular cell adhesion molecule (VCAM)-1 during leukocyte adhesion and transendothelial migration (TEM). VCAM-1 interacted directly with moesin and ezrin in vitro, and all of these molecules colocalized at the apical surface of endothelium. Dynamic assessment of this interaction in living cells showed that both VCAM-1 and moesin were involved in lymphoblast adhesion and spreading on the endothelium, whereas only moesin participated in TEM, following the same distribution pattern as ICAM-1. During leukocyte adhesion in static or under flow conditions, VCAM-1, ICAM-1, and activated moesin and ezrin clustered in an endothelial actin-rich docking structure that anchored and partially embraced the leukocyte containing other cytoskeletal components such as α-actinin, vinculin, and VASP. Phosphoinositides and the Rho/p160 ROCK pathway, which participate in the activation of ERM proteins, were involved in the generation and maintenance of the anchoring structure. These results provide the first characterization of an endothelial docking structure that plays a key role in the firm adhesion of leukocytes to the endothelium during inflammation.
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