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Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling

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Huveneers, Stephan, Oldenburg, Joppe, Spanjaard, Emma, van der Krogt, Gerard, Grigoriev, Ilya, Akhmanova, Anna, Rehmann, Holger, de Rooij, Johan·2012·Journal of Cell Biology
DOI 10.1083/jcb.201108120PMC PMC3307691
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Abstract

To remodel endothelial cell–cell adhesion, inflammatory cytokine- and angiogenic growth factor–induced signals impinge on the vascular endothelial cadherin (VE-cadherin) complex, the central component of endothelial adherens junctions. This study demonstrates that junction remodeling takes place at a molecularly and phenotypically distinct subset of VE-cadherin adhesions, defined here as focal adherens junctions (FAJs). FAJs are attached to radial F-actin bundles and marked by the mechanosensory protein Vinculin. We show that endothelial hormones vascular endothelial growth factor, tumor necrosis factor α, and most prominently thrombin induced the transformation of stable junctions into FAJs. The actin cytoskeleton generated pulling forces specifically on FAJs, and inhibition of Rho-Rock-actomyosin contractility prevented the formation of FAJs and junction remodeling. FAJs formed normally in cells expressing a Vinculin binding-deficient mutant of α-catenin, showing that Vinculin recruitment is not required for adherens junction formation. Comparing Vinculin-devoid FAJs to wild-type FAJs revealed that Vinculin protects VE-cadherin junctions from opening during their force-dependent remodeling. These findings implicate Vinculin-dependent cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis.

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Authors
Huveneers, S., Oldenburg, J., Spanjaard, E., van der Krogt, G., Grigoriev, I., Akhmanova, A., Rehmann, H., & de Rooij, J.
Affiliations
  • University Medical Center Utrecht (NL)
  • Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, 3584 CT, Utrecht, Netherlands 1
  • Utrecht University (NL)
Corresponding author
Huveneers, Stephan
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2012-03-05
Volume
196
Issue
5
Pages
641-652
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201108120
PMC
PMC3307691
OpenAlex
W2119658007
Cited by
481
References
0
Citations by year
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FWCI
21.05
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (863.10.003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
vinculin, VE-cadherin, adherens junctions, junction remodeling, mechanosensing, thrombin, vascular endothelial growth factor, TNF-α, alpha-catenin, actin cytoskeleton, leukocyte transmigration, angiogenesis
MeSH terms
Cadherin 5, Actins, Cytoskeletal Proteins, Cytoskeleton, Endothelium, Vascular, Humans, Recombinant Fusion Proteins, Stress, Mechanical, Thrombin, Tumor Necrosis Factor-alpha, Antigens, CD, Cadherins, Vinculin, Adherens Junctions, Mechanotransduction, Cellular, Vascular Endothelial Growth Factor A, Endothelial Cells, Human Umbilical Vein Endothelial Cells

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