Signaling Mechanism Involved in Regulation of Endothelial Cell-Cell Junctions

被引:1
作者
Fukuhara, Shigetomo [1 ]
Mochizuki, Naoki [1 ]
机构
[1] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Cell Biol, Osaka 5658565, Japan
来源
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN | 2010年 / 130卷 / 11期
关键词
endothelial permeability; vascular endothelial-cadherin; Rapl; actin; alpha-catenin; RAP1; EFFECTOR; BETA-CATENIN; CADHERIN; ANGIOPOIETIN-1; ACTIVATION; ADHESION; CONTACTS; PROTEIN; GTPASE; TIE2;
D O I
10.1248/yakushi.130.1413
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Endothelial cells lining blood vessels are in tight contact with each other, thereby maintaining vascular integrity. Compromising vascular integrity leads to an increase in vascular permeability, which is associated with chronic inflammation, edema, and tumor angiogenesis. Vascular endothelial (VE) -cadherin is an endothelium-specific cell-cell adhesion molecule involved in endothelial barrier functions. We previously reported that cyclic AMP-elevating agonists such as prostaglandins and adrenomedullin potentiate VE-cadherin-dependent cell adhesion by inducing activation of Rap1 small GTPase through Epac. We further investigated the mechanism whereby Rap1 potentiates VE-cadherin-dependent cell adhesion, and found that Rap1 induces the formation of circumferential actin bundles along the cell-cell junctions. Although it has been believed that alpha-/beta-catenins anchor cadherin to the actin cytoskeleton to stabilize cadherin at cell-cell junctions (classical model), Nelson's and Weis' groups have recently suggested a new dynamic model in which alpha-/beta-catenins do not stably connect actin to cadherin. However, our study clearly indicated that the circumferential actin bundles anchor VE-cadherin to the cell-cell junctions through alpha-/beta-catenins. Thus Rap1 potentiates endothelial cell-cell junctions through the mechanism based on the static model.
引用
收藏
页码:1413 / 1420
页数:8
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