Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization.
Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization.
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DOI：
10.1083/jcb.140.6.1475
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发表时间：
1998-03-23
期刊：
影响因子：
--
通讯作者：
Dejana E
中科院分区：
文献类型：
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作者：
Navarro P;Ruco L;Dejana E
内皮细胞的两种主要钙粘蛋白是神经（N）-钙粘蛋白和血管内皮（VE）-钙粘蛋白。尽管蛋白质表达水平相似，但只有VE-钙粘蛋白位于细胞-细胞接触处，而N-钙粘蛋白分布在整个细胞膜上。在CHO细胞中共转染VE-钙粘蛋白和N-钙粘蛋白导致与在内皮细胞中观察到的相同的分布，表明这两种钙粘蛋白的行为不是细胞特异性的，而是与它们的结构特征有关。相似量的α-和β-连环蛋白和斑珠蛋白与VE-和N-钙粘蛋白相关，而p120在VE-钙粘蛋白复合物中更高。VE-钙粘蛋白的存在并不影响N-钙粘蛋白的同型粘附特性或其能力，当共转染子与仅转染N-钙粘蛋白的细胞共培养时，定位在连接处。为了确定负责VE-钙粘蛋白显性活性的分子结构域，我们制备了由VE-钙粘蛋白胞外区连接至N-钙粘蛋白胞内结构域形成的嵌合构建体。嵌合体失去了从连接处排除N-钙粘蛋白的能力，表明单独的VE-钙粘蛋白的细胞外结构域不足以使分子优先定位在连接处。VE-钙粘蛋白的截短突变体保留完整的细胞外结构域和短的胞质尾（Arg 621-Pro702）缺乏连环蛋白结合区，能够排除N-钙粘蛋白的连接。这表明VE-钙粘蛋白胞质尾区中的Arg 621-Pro702序列是N-钙粘蛋白从连接处排除所需的。以前从未描述过钙粘蛋白在同一细胞中的细胞间连接处聚集的竞争。我们推测，在内皮，VE-和N-钙粘蛋白发挥不同的作用，而VE-钙粘蛋白主要促进内皮细胞之间的同型相互作用，N-钙粘蛋白可能是负责锚定的内皮细胞周围的其他细胞类型表达N-钙粘蛋白，如血管平滑肌细胞或周细胞。
The two major cadherins of endothelial cells are neural (N)-cadherin and vascular endothelial (VE)- cadherin. Despite similar level of protein expression only VE-cadherin is located at cell–cell contacts, whereas N-cadherin is distributed over the whole cell membrane. Cotransfection of VE-cadherin and N-cadherin in CHO cells resulted in the same distribution as that observed in endothelial cells indicating that the behavior of the two cadherins was not cell specific but related to their structural characteristics. Similar amounts of α- and β-catenins and plakoglobin were associated to VE- and N-cadherins, whereas p120 was higher in the VE-cadherin complex. The presence of VE-cadherin did not affect N-cadherin homotypic adhesive properties or its capacity to localize at junctions when cotransfectants were cocultured with cells transfected with N-cadherin only. To define the molecular domain responsible for the VE-cadherin–dominant activity we prepared a chimeric construct formed by VE-cadherin extracellular region linked to N-cadherin intracellular domain. The chimera lost the capacity to exclude N-cadherin from junctions indicating that the extracellular domain of VE-cadherin alone is not sufficient for the preferential localization of the molecule at the junctions. A truncated mutant of VE-cadherin retaining the full extracellular domain and a short cytoplasmic tail (Arg621–Pro702) lacking the catenin-binding region was able to exclude N-cadherin from junctions. This indicates that the Arg621–Pro702 sequence in the VE-cadherin cytoplasmic tail is required for N-cadherin exclusion from junctions. Competition between cadherins for their clustering at intercellular junctions in the same cell has never been described before. We speculate that, in the endothelium, VE- and N-cadherin play different roles; whereas VE-cadherin mostly promotes the homotypic interaction between endothelial cells, N-cadherin may be responsible for the anchorage of the endothelium to other surrounding cell types expressing N-cadherin such as vascular smooth muscle cells or pericytes.