In:
Journal of Cell Science, The Company of Biologists
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2015
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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