VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells
VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells
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DOI：
10.1074/jbc.m212591200
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发表时间：
2003-05-02
影响因子：
4.8
通讯作者：
Malik, AB
中科院分区：
文献类型：
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作者：
Kouklis, P;Konstantoulaki, M;Malik, AB
钙粘蛋白的细胞质结构域和相关的连环蛋白通过信号转导途径连接细胞骨架。为了研究非连接型VE-cadherin的信号功能，我们在亚融合内皮细胞中表达野生型VE-cadherin或VE-cadherin细胞质结构域（DeltaEXD）。我们观察到Cdc42在转染的细胞中被激活，这些细胞也产生了Cdc42依赖的bbb70毫米长的质膜突起。这些结构的形成需要肌动蛋白聚合，与上皮细胞相比，它们在内皮细胞中特异性地发育。缺乏β -连环蛋白结合位点的VE-cadherin细胞质结构域的表达也诱导Cdc42活化；因此，它的激活不能归因于β -连环蛋白的结合。然而，这些细胞不能形成突起。这些结果表明，非连接型ve -钙粘蛋白的细胞质结构域可以作为参与内皮质膜Cdc42激活的支架。-连环蛋白和相关的-连环蛋白可能作为肌动蛋白聚合的支持位点，导致长质膜突起的形成。因此，非连接性ve -钙粘蛋白积极参与质膜的内向外信号传导，导致内皮膜突起的发生。
The cytoplasmic domain of cadherins and the associated catenins link the cytoskeleton with signal transduction pathways. To study the signaling function of non-junctional VE-cadherin, which can form during the loss VE-cadherin homotypic adhesion, wild type VE-cadherin or VE-cadherin cytoplasmic domain (DeltaEXD) was expressed in sub-confluent endothelial cells. We observed that Cdc42 was activated in transfected cells and that these cells also developed Cdc42-dependent >70-mum-long plasma membrane protrusions. The formation of these structures required actin polymerization, and they developed specifically in endothelial cells as compared with epithelial cells. Expression of the VE-cadherin cytoplasmic domain lacking the beta-catenin binding site also induced Cdc42 activation; thus, its activation cannot be ascribed to beta-catenin binding. However, these cells were not able to form the protrusions. These results suggest that the cytoplasmic domain of non-junctional VE-cadherin can serve as a scaffold involved in Cdc42 activation at the endothelial plasma membrane. beta-Catenin and the associated alpha-catenin may serve as support sites for actin polymerization, leading to formation of long plasma membrane protrusions. Thus, non-junctional VE-cadherin actively participates in inside-out signaling at the plasma membrane, leading to the development of endothelial membrane protrusions.