Lung Biology Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Microvasc Res. 2012 Jan;83(1):3-11. doi: 10.1016/j.mvr.2011.08.001. Epub 2011 Aug 16.
A layer of endothelial cells attached to their underlying matrices by complex transmembrane structures termed focal adhesion (FA) proteins maintains the barrier property of microvascular endothelium. FAs sense the physical properties of the extracellular matrix (ECM) and organize the cytoskeleton accordingly. The close association of adherens junction (AJ) protein, cadherin, with the cytoskeleton is known to be essential in coordinating the appropriate mechanical properties to cell-cell contacts. Recently, it has become clear that a crosstalk exists between focal adhesion kinase (FAK) and cadherin that regulates signaling at intercellular endothelial junctions. This review discusses recent advances in our understanding of the dynamic regulation of the molecular connections between FAK and the cadherin complex and cadherin-catenin-actin interaction-dependent changes as well as the role of small GTPases in endothelial barrier regulation. This review also discusses how a signaling network regulates a range of cellular processes important for barrier function and diseases.
一层内皮细胞通过称为黏着斑(FA)蛋白的复杂跨膜结构附着在其下的基质上,维持微血管内皮的屏障特性。FA 感知细胞外基质(ECM)的物理特性,并相应地组织细胞骨架。众所周知,黏着连接(AJ)蛋白钙黏蛋白与细胞骨架的紧密关联对于协调适当的机械特性至关重要细胞-细胞接触。最近,已经清楚的是,黏着斑激酶(FAK)和钙黏蛋白之间存在串扰,调节细胞间内皮连接处的信号转导。这篇综述讨论了我们对 FAK 与钙黏蛋白复合物之间分子连接的动态调节以及钙黏蛋白-连环蛋白-肌动蛋白相互作用依赖性变化的理解的最新进展,以及小 GTPase 在血管内皮屏障调节中的作用。这篇综述还讨论了信号网络如何调节一系列对屏障功能和疾病很重要的细胞过程。