Contribution of annexin 2 to the architecture of mature endothelial adherens junctions
Contribution of annexin 2 to the architecture of mature endothelial adherens junctions
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DOI：
10.1128/mcb.00695-07
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发表时间：
2008-03-01
影响因子：
5.3
通讯作者：
Gulino-Debrac, Danielle
中科院分区：
文献类型：
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作者：
Heyraud, Stephanie;Jaquinod, Michel;Gulino-Debrac, Danielle
基于血管内皮钙粘蛋白（VE-cad）的复合物参与维持血管内皮完整性。使用免疫沉淀实验，我们已经证明，在汇合的人脐静脉内皮细胞，VE-钙粘蛋白为基础的复合物与膜联蛋白2和膜联蛋白2易位从细胞质的细胞-细胞接触部位细胞汇合成立。位于胆固醇筏中的膜联蛋白2与肌动蛋白细胞骨架和基于VE-cad的复合物结合，因此复合物与胆固醇筏对接。这些多重连接防止了基于VE-cad的复合物的侧向扩散，从而在成熟的最终步骤中加强了粘附连接。此外，我们观察到小干扰RNA下调膜联蛋白2诱导VE-cad从粘附连接处的离域，从而使这些连接处不稳定。此外，我们的数据表明，解耦的膜联蛋白2/p11复合物从VE-cad为基础的连接，血管内皮生长因子治疗触发，促进从静止到不成熟状态的切换。
The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.