Vinculin strengthens the endothelial barrier during vascular development

in Vascular Biology
Authors:
Miesje M. van der StoelM van der Stoel, Department of Medical Biochemistry, University of Amsterdam, Amsterdam, Netherlands

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Maria P. KotiniM Kotini, Biozentrum - The Center for Molecular Life Sciences, Basel, Switzerland

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Rianne M. SchoonR Schoon, Department of Medical Biochemistry, University of Amsterdam, Amsterdam, Netherlands

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Markus AffolterM Affolter, Biozentrum - The Center for Molecular Life Sciences, Basel, Switzerland

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Heinz-Georg BeltingH Belting, Biozentrum - The Center for Molecular Life Sciences, Basel, Switzerland

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Stephan HuveneersS Huveneers, Department of Medical Biochemistry, University of Amsterdam, Amsterdam, 1000 GG, Netherlands

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Correspondence: Stephan Huveneers, Email: s.huveneers@amsterdamumc.nl
Open access

Remodelling of cell-cell junctions is crucial for proper tissue development and barrier function. The Cadherin-based adherens junctions anchor via β-Catenin and α-Catenin to the actomyosin cytoskeleton, together forming a junctional mechanotransduction complex. Tension-induced conformational changes in the mechanosensitive α-Catenin protein induce junctional Vinculin recruitment. In endothelial cells, Vinculin protects the remodelling VE-Cadherin junctions. In this study, we have addressed the role of Vinculin in endothelial barrier function in the developing vasculature. In vitro experiments, using endothelial cells in which α-Catenin was replaced by a Vinculin-binding deficient mutant, showed that junctional recruitment of Vinculin promotes endothelial barrier function. To assess the role of Vinculin within blood vessels in vivo, we next investigated barrier function in the vasculature of Vinculin knockout zebrafish. In the absence of Vinculin, sprouting angiogenesis and vessel perfusion still occurred. Intriguingly, the absence of Vinculin made the blood vessels more permeable for 10 kDa dextran molecules, but not for larger tracers. Taken together, our findings demonstrate that Vinculin strengthens the endothelial barrier and prevents vascular leakage in developing vessels.

 

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