Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 387, Issue 1-2, Pages 39-53Publisher
SPRINGER
DOI: 10.1007/s11010-013-1867-4
Keywords
T-cadherin; VE-cadherin; Endothelial permeability; Rho GTPases
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Funding
- Welcome Trust [075154/Z/04/Z]
- Russian Foundation for Basic Research [08-04-01024-a]
- Russian Government [16.512.11.2262]
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T-cadherin is a unique member of the cadherin superfamily of adhesion molecules. In contrast to classical cadherins, T-cadherin lacks transmembrane and cytoplasmic domains and is anchored to the cell membrane via a glycosilphosphoinositol moiety. T-cadherin is predominantly expressed in cardiovascular system. Clinical and biochemical studies evidence that expression of T-cadherin increases in post-angioplasty restenosis and atherosclerotic lesions-conditions associated with endothelial dysfunction and pathological expression of adhesion molecules. Here, we provide data suggesting a new signaling mechanism by which T-cadherin regulates endothelial permeability. T-cadherin overexpression leads to VE-cadherin phosphorylation on Y731 (beta-catenin-binding site), VE-cadherin clathrin-dependent endocytosis and its degradation in lysosomes. Moreover, T-cadherin overexpression results in activation of Rho GTPases signaling and actin stress fiber formation. Thus, T-cadherin up-regulation is involved in degradation of a key endothelial adhesion molecule, VE-cadherin, resulting in the disruption of endothelial barrier function. Our results point to the role of T-cadherin in regulation of endothelial permeability and its possible engagement in endothelial dysfunction.
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