J. van Rijssel
J. van Unen
J.D. van Buul
- A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1
- Journal of Cell Science
- Volume | Issue number
- 128 | 16
- Pages (from-to)
- Document type
- Faculty of Medicine (AMC-UvA)
Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
Endothelial cell-cell junctions maintain a restrictive barrier that is tightly regulated to allow dynamic responses to permeability-inducing angiogenic factors as well as inflammatory agents and adherent leukocytes. The ability of these stimuli to transiently remodel adherens junctions (AJs) depends on Rho-GTPase-controlled cytoskeletal rearrangements. How activity of Rho-GTPases is spatio-temporally controlled at endothelial AJs by guanine-nucleotide exchange factors (GEFs) is incompletely understood. Here, we identify a crucial role for the Rho-GEF Trio in stabilizing VE-cadherin-based junctions. Trio interacts with VE-cadherin and locally activates Rac1 at AJs during nascent contact formation, assessed using a novel FRET-based Rac1 biosensor and biochemical assays. The Rac-GEF domain of Trio is responsible for remodeling of junctional actin from radial to cortical actin bundles, a critical step for junction stabilization. This promotes the formation of linear AJs and increases endothelial monolayer resistance. Collectively, our data show the importance of spatio-temporal regulation of the actin cytoskeleton through Trio and Rac1 at VE-cadherin-based cell-cell junctions to maintain the endothelial barrier.
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- With supplemental figures. - Erratum in Journal of Cell Science, vol. 128 no. 18.
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