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Vinculin strengthens the endothelial barrier during vascular development

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...

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Autores principales: van der Stoel, Miesje M, Kotini, Maria P, Schoon, Rianne M, Affolter, Markus, Belting, Heinz-Georg, Huveneers, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986378/
https://www.ncbi.nlm.nih.gov/pubmed/36260739
http://dx.doi.org/10.1530/VB-22-0012
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author van der Stoel, Miesje M
Kotini, Maria P
Schoon, Rianne M
Affolter, Markus
Belting, Heinz-Georg
Huveneers, Stephan
author_facet van der Stoel, Miesje M
Kotini, Maria P
Schoon, Rianne M
Affolter, Markus
Belting, Heinz-Georg
Huveneers, Stephan
author_sort van der Stoel, Miesje M
collection PubMed
description 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 of 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 vcl 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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spelling pubmed-99863782023-03-07 Vinculin strengthens the endothelial barrier during vascular development van der Stoel, Miesje M Kotini, Maria P Schoon, Rianne M Affolter, Markus Belting, Heinz-Georg Huveneers, Stephan Vasc Biol Research 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 of 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 vcl 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. Bioscientifica Ltd 2022-10-19 /pmc/articles/PMC9986378/ /pubmed/36260739 http://dx.doi.org/10.1530/VB-22-0012 Text en © The authors https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. (https://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle Research
van der Stoel, Miesje M
Kotini, Maria P
Schoon, Rianne M
Affolter, Markus
Belting, Heinz-Georg
Huveneers, Stephan
Vinculin strengthens the endothelial barrier during vascular development
title Vinculin strengthens the endothelial barrier during vascular development
title_full Vinculin strengthens the endothelial barrier during vascular development
title_fullStr Vinculin strengthens the endothelial barrier during vascular development
title_full_unstemmed Vinculin strengthens the endothelial barrier during vascular development
title_short Vinculin strengthens the endothelial barrier during vascular development
title_sort vinculin strengthens the endothelial barrier during vascular development
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986378/
https://www.ncbi.nlm.nih.gov/pubmed/36260739
http://dx.doi.org/10.1530/VB-22-0012
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