Homoassociation of VE-cadherin follows a mechanism common to "classical" cadherins
Homoassociation of VE-cadherin follows a mechanism common to "classical" cadherins
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DOI：
10.1016/s0022-2836(02)01286-x
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发表时间：
2003-01-24
影响因子：
5.6
通讯作者：
Engel, J
中科院分区：
文献类型：
--
作者：
Ahrens, T;Lambert, M;Engel, J
血管内皮细胞钙粘蛋白(VE-cadherin/cadherin5)特异性表达于内皮细胞间的黏附连接，在细胞间黏附和信号转导中发挥重要作用。为了分析VE-钙粘蛋白同源结合的机制，通过连接子序列将胞外结构域CAD1-5连接到软骨基质蛋白卷曲线圈结构域(CMP)的N端。嵌合体VECADCMP在哺乳动物细胞中表达。三聚螺旋线圈结构域导致高的本征结构域浓度和促进自缔合的多价性。在固相分析和交联实验中检测到VECADCMP的Ca“依赖的同亲缔合。当用电子显微镜分析VECADCMP中的相互作用以及这些三聚体蛋白之间的相互作用时，观察到了与E、N或P-钙粘蛋白等1型(“经典”)钙粘蛋白的同源关联的惊人相似之处。依赖于钙离子的环状和双环状排列表明胞外结构域1和2之间存在相互作用，这可能与黏附过程中的侧向接触和粘连接触有关。通过化学交联法也证实了两个VECADCMP分子组成的络合物的缔合作用。没有迹象表明VECAD胞外区与六聚体复合体的反平行关联是由Legrand等人提出的。被发现了。相反，数据表明VE-钙粘蛋白的同源关联遵循I型钙粘蛋白的保守机制。(C)2003爱思唯尔科学有限公司。保留所有权利
Vascular endothelial cadherin (VE-cadherin/cadherin5) is specifically expressed in adherens junctions of endothelial cells and exerts important functions in cell-cell adhesion as well as signal transduction. To analyze the mechanism of VE-cadherin homoassociation, the ectodomains CAD1-5 were connected by linker sequences to the N terminus of the coiled-coil domain of cartilage matrix protein (CMP). The chimera VECADCMP were expressed in mammalian cells. The trimeric coiled-coil domain leads to high intrinsic domain concentrations and multivalency promoting self-association. Ca"-dependent homophilic association of VECADCMP was detected in solid phase assays and crosslinking experiments. A striking analogy to homoassociation of type 1 ("classical") cadherins like E, N or P-cadherin was observed when interactions in VECADCMP and between these trimeric proteins were analyzed by electron microscopy. Ca2+-dependent ring-like and double ring-like arrangements suggest interactions between domains 1 and 2 of the ectodomains, which may be correlated with lateral and adhesive contacts in the adhesion process. Association to complexes composed of two VECADCMP molecules was also demonstrated by chemical cross-linking. No indication for an antiparallel association of VECAD ectodomains to hexameric complexes as proposed by Legrand et al. was found. Instead the data suggest that homoassociation of VE-cadherin follows the conserved mechanism of type I cadherins. (C) 2003 Elsevier Science Ltd. All rights reserved