Titre
Caveolin-1 opens endothelial cell junctions by targeting catenins.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kronstein, R.
Auteure/Auteur
Seebach, J.
Auteure/Auteur
Grossklaus, S.
Auteure/Auteur
Minten, C.
Auteure/Auteur
Engelhardt, B.
Auteure/Auteur
Drab, M.
Auteure/Auteur
Liebner, S.
Auteure/Auteur
Arsenijevic, Y.
Auteure/Auteur
Taha, A.A.
Auteure/Auteur
Afanasieva, T.
Auteure/Auteur
Schnittler, H.J.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1755-3245
Statut éditorial
Publié
Date de publication
2012
Volume
93
Numéro
1
Première page
130
Dernière page/numéro d’article
140
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.
Sujets
PID Serval
serval:BIB_CCF339084AD6
PMID
Open Access
Oui
Date de création
2012-06-04T10:12:25.881Z
Date de création dans IRIS
2025-05-20T22:19:43Z
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Nom
REF.pdf
Version du manuscrit
published
Taille
838.95 KB
Format
Adobe PDF
PID Serval
serval:BIB_CCF339084AD6.P001
URN
urn:nbn:ch:serval-BIB_CCF339084AD60
Somme de contrôle
(MD5):87357fcb8745806e441e8c36a77380f8