Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells.
Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells.
复制标题
钙粘蛋白和PECAM-1之间的空间和时间关系在人内皮细胞的细胞 - 细胞连接处。
DOI：
10.1083/jcb.126.1.247
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发表时间：
1994-07
影响因子：
7.8
通讯作者：
Geiger, B
中科院分区：
文献类型：
--
作者：
Ayalon, O;Sabanai, H;Lampugnani, M G;Dejana, E;Geiger, B
内衬整个血管系统腔的内皮层的完整性取决于细胞与下面的基底膜以及彼此之间的紧密粘附。之前已经证明，这种相互作用是通过膜受体发生的，这些受体决定了表面粘附的特异性、拓扑结构和机械性能。内皮细胞之间的细胞-细胞连接，在培养和原位，涉及钙（2+）依赖性和非依赖性的机制，是由不同的粘附分子介导的。Ca（2+）依赖的细胞间粘附主要通过钙粘蛋白家族的成员发生，在粘附连接中，钙粘蛋白家族将微丝系统局部锚在质膜上。据报道，非钙依赖性粘连主要涉及IG超家族成员。在这项研究中，我们进行了三维显微镜分析这两个内皮细胞间粘附系统的相对亚细胞分布。我们发现，钙粘蛋白位于相邻的（通常更顶端），但明显不同的领域的侧质膜相比，PECAM-1。此外，钙粘蛋白在接种内皮细胞后2 h内首先在粘附连接处组织化，形成多个侧斑，这些侧斑在24 h内发展成广泛的带状结构。PECAM-1与表面粘连显著相关，并逐渐与含钙粘蛋白的粘连相关。钙粘蛋白和PECAM-1也在其去污剂可提取性方面不同，反映了它们与细胞骨架的结合模式的差异。此外，这两个粘附系统可以差异调制，因为短的治疗与钙离子螯合剂EGTA，破坏了钙粘蛋白连接，留下PECAM-1明显完整。这些结果证实，内皮细胞具有不同的细胞间接触机制，在他们的空间和时间组织，以及在他们的功能特性。
The integrity of the endothelial layer, which lines the entire cavity of the vascular system, depends on tight adhesion of the cells to the underlying basement membrane as well as to each other. It has been previously shown that such interactions occur via membrane receptors that determine the specificity, topology, and mechanical properties of the surface adhesion. Cell-cell junctions between endothelial cells, in culture and in situ, involve both Ca(2+)-dependent and -independent mechanisms that are mediated by distinct adhesion molecules. Ca(2+)- dependent cell-cell adhesion occurs mostly via members of the cadherin family, which locally anchor the microfilament system to the plasma membrane, in adherens junctions. Ca(2+)-independent adhesions were reported to mainly involve members of the Ig superfamily. In this study, we performed three-dimensional microscopic analysis of the relative subcellular distributions of these two endothelial intercellular adhesion systems. We show that cadherins are located at adjacent (usually more apical), yet clearly distinct domains of the lateral plasma membrane, compared to PECAM-1. Moreover, cadherins were first organized in adherens junctions within 2 h after seeding of endothelial cells, forming multiple lateral patches which developed into an extensive belt-like structure over a period of 24 h. PECAM-1 became associated with surface adhesions significantly later and became progressively associated with the cadherin-containing adhesions. Cadherins and PECAM-1 also differed in their detergent extractability, reflecting differences in their mode of association with the cytoskeleton. Moreover, the two adhesion systems could be differentially modulated since short treatment with the Ca2+ chelator EGTA, disrupted the cadherin junctions leaving PECAM-1 apparently intact. These results confirm that endothelial cells possess distinct intercellular contact mechanisms that differ in their spatial and temporal organization as well as in their functional properties.