PUBLICATION

Vinculin controls endothelial cell junction dynamics during vascular lumen formation

Authors
Kotini, M.P., van der Stoel, M.M., Yin, J., Han, M.K., Kirchmaier, B., de Rooij, J., Affolter, M., Huveneers, S., Belting, H.G.
ID
ZDB-PUB-220414-8
Date
2022
Source
Cell Reports   39: 110658 (Journal)
Registered Authors
Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Huveneers, Stephan, Kirchmaier, Bettina, van der Stoel, Miesje
Keywords
CP: Cell biology, VE-cadherin, angiogenesis, cell-cell adhesion, junctional dynamics, lumenization, vinculin, zebrafish
MeSH Terms
  • Adherens Junctions/metabolism
  • Animals
  • Cadherins/metabolism
  • Endothelial Cells*/metabolism
  • Intercellular Junctions/metabolism
  • Mechanotransduction, Cellular*
  • Neovascularization, Physiologic
  • Vinculin*/metabolism
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
PubMed
35417696 Full text @ Cell Rep.
Abstract
Blood vessel morphogenesis is driven by coordinated endothelial cell behaviors. Active remodeling of cell-cell junctions promotes cellular plasticity while preserving vascular integrity. Here, we analyze the dynamics of endothelial adherens junctions during lumen formation in angiogenic sprouts in vivo. Live imaging in zebrafish reveals that lumen expansion is accompanied by the formation of transient finger-shaped junctions. Junctional fingers are positively regulated by blood pressure, whereas flow inhibition prevents their formation. Using fluorescent reporters, we show that junctional fingers contain the mechanotransduction protein vinculin. Furthermore, genetic deletion of vinculin prevents finger formation, a junctional defect that could be rescued by transient endothelial expression of vinculin. Our findings suggest a mechanism whereby lumen expansion leads to an increase in junctional tension, triggering recruitment of vinculin and formation of junctional fingers. We propose that endothelial cells employ force-dependent junctional remodeling to counteract external forces in order to maintain vascular integrity during sprouting angiogenesis.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
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Errata and Notes