Navarro P, Caveda L, Breviario F, Mândoteanu I, Lampugnani M G, Dejana E
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italia.
J Biol Chem. 1995 Dec 29;270(52):30965-72. doi: 10.1074/jbc.270.52.30965.
Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial specific cadherin that regulates cell to cell junction organization in this cell type. Cadherin linkage to intracellular catenins was found to be required for their adhesive properties and for localization at cell to cell junctions. We constructed a mutant form of VE-cadherin lacking the last 82 amino acids of the cytoplasmic domain. Surprisingly, despite any detectable association of this truncated VE-cadherin to catenin-cytoskeletal complex, the molecule was able to cluster at cell-cell contacts in a manner similar to wild type VE-cadherin. Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migration from a confluent monolayer. In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain. These results suggest that the VE-cadherin extracellular domain is enough for early steps of cell adhesion and recognition. However, interaction of VE-cadherin with the cytoskeleton is necessary to provide strength and cohesion to the junction. The data also suggest that cadherin functional regulation might not be identical among the members of the family.
血管内皮钙黏蛋白（VE-钙黏蛋白、钙黏蛋白-5或7B4）是一种内皮细胞特异性钙黏蛋白，可调节该细胞类型中的细胞间连接组织。已发现钙黏蛋白与细胞内连环蛋白的连接对于它们的黏附特性以及在细胞间连接处的定位是必需的。我们构建了一种VE-钙黏蛋白的突变形式，该形式缺失细胞质结构域的最后82个氨基酸。令人惊讶的是，尽管这种截短的VE-钙黏蛋白与连环蛋白-细胞骨架复合物没有任何可检测到的关联，但该分子仍能够以类似于野生型VE-钙黏蛋白的方式在细胞-细胞接触处聚集。截短的VE-钙黏蛋白还能够促进钙依赖性细胞间聚集，并部分抑制细胞从汇合单层的脱离和迁移。相反，VE-钙黏蛋白细胞质结构域的截短严重损害了细胞间连接对高分子量分子的通透性。这些结果表明，VE-钙黏蛋白的细胞外结构域足以完成细胞黏附和识别的早期步骤。然而，VE-钙黏蛋白与细胞骨架的相互作用对于为连接提供强度和凝聚力是必要的。数据还表明，钙黏蛋白家族成员之间的功能调节可能并不相同。
