Fulltext

Caveolin-1 opens endothelial cell junctions by targeting catenins

Kronstein, Romy ; Seebach, Jochen ; Großklaus, Sylvia ; Minten, Carsten ; Engelhardt, Britta ; Drab, Marek ; Liebner, Stefan ; Arsenijevic, Yvan ; Taha, Abdallah Abu ; Afanasieva, Tatiana ; Schnittler, Hans-Joachim

In: Cardiovascular Research, 2012, vol. 93, no. 1, p. 130-140

Aggiungi alla tua lista
    Titre
    • Caveolin-1 opens endothelial cell junctions by targeting catenins
    Auteur
    • Kronstein, Romy. Institute of Physiology, Medical Faculty of the TU-Dresden, Dresden, Germany
    • Seebach, Jochen. Institute of Anatomy and Vascular Biology, Vesaliusweg 2-4, Westfälische Wilhelms-University of Münster, Münster, Germany
    • Großklaus, Sylvia. Institute of Physiology, Medical Faculty of the TU-Dresden, Dresden, Germany
    • Minten, Carsten. Theodor Kocher Institute, University of Bern, Bern, Switzerland
    • Engelhardt, Britta. Theodor Kocher Institute, University of Bern, Bern, Switzerland
    • Drab, Marek. Institute of Immunology and Experimental Therapy, Wroclaw, Poland
    • Liebner, Stefan. Institute of Neurology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany
    • Arsenijevic, Yvan. Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
    • Taha, Abdallah Abu. Institute of Anatomy and Vascular Biology, Vesaliusweg 2-4, Westfälische Wilhelms-University of Münster, Münster, Germany
    • Afanasieva, Tatiana. Institute of Physiology, Medical Faculty of the TU-Dresden, Dresden, Germany
    • Schnittler, Hans-Joachim. Institute of Anatomy and Vascular Biology, Vesaliusweg 2-4, Westfälische Wilhelms-University of Münster, Münster, Germany
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Cardiovascular Research, 2012, vol. 93, no. 1, p. 130-140. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299327
    Summary
    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