Caveolin-1 opens endothelial cell junctions by targeting catenins.

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Serval ID
serval:BIB_CCF339084AD6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Caveolin-1 opens endothelial cell junctions by targeting catenins.
Journal
Cardiovascular Research
Author(s)
Kronstein R., Seebach J., Grossklaus S., Minten C., Engelhardt B., Drab M., Liebner S., Arsenijevic Y., Taha A.A., Afanasieva T., Schnittler H.J.
ISSN
1755-3245 (Electronic)
ISSN-L
0008-6363
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
93
Number
1
Pages
130-140
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
AIMS: A fundamental phenomenon in inflammation is the loss of endothelial barrier function, in which the opening of endothelial cell junctions plays a central role. However, the molecular mechanisms that ultimately open the cell junctions are largely unknown.¦METHODS AND RESULTS: Impedance spectroscopy, biochemistry, and morphology were used to investigate the role of caveolin-1 in the regulation of thrombin-induced opening of cell junctions in cultured human and mouse endothelial cells. Here, we demonstrate that the vascular endothelial (VE) cadherin/catenin complex targets caveolin-1 to endothelial cell junctions. Association of caveolin-1 with VE-cadherin/catenin complexes is essential for the barrier function decrease in response to the pro-inflammatory mediator thrombin, which causes a reorganization of the complex in a rope ladder-like pattern accompanied by a loss of junction-associated actin filaments. Mechanistically, we show that in response to thrombin stimulation the protease-activated receptor 1 (PAR-1) causes phosphorylation of caveolin-1, which increasingly associates with β- and γ-catenin. Consequently, the association of β- and γ-catenin with VE-cadherin is weakened, thus allowing junction reorganization and a decrease in barrier function. Thrombin-induced opening of cell junctions is lost in caveolin-1-knockout endothelial cells and after expression of a Y/F-caveolin-1 mutant but is completely reconstituted after expression of wild-type caveolin-1.¦CONCLUSION: Our results highlight the pivotal role of caveolin-1 in VE-cadherin-mediated cell adhesion via catenins and, in turn, in barrier function regulation.
Keywords
Animals, Antigens, CD/metabolism, Base Sequence, CHO Cells, Cadherins/metabolism, Catenins/metabolism, Caveolin 1/deficiency, Caveolin 1/genetics, Cell Line, Cricetinae, Cricetulus, DNA Primers/genetics, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Human Umbilical Vein Endothelial Cells, Humans, Intercellular Junctions/drug effects, Intercellular Junctions/metabolism, Mice, Mice, Knockout, Multiprotein Complexes/metabolism, Mutant Proteins/genetics, Mutant Proteins/metabolism, Thrombin/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
04/06/2012 12:12
Last modification date
25/09/2019 7:10
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