Dataset Information

N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability.

ABSTRACT: Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin (Cdh2) in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs. N-cadherin functions by increasing the rate of VE-cadherin recruitment to AJs and induces the assembly of VE-cadherin junctions. We identified the dual Rac1/RhoA Rho guanine nucleotide exchange factor (GEF) Trio as a critical component of the N-cadherin adhesion complex, which activates both Rac1 and RhoA signaling pathways at AJs. Trio GEF1-mediated Rac1 activation induces the recruitment of VE-cadherin to AJs, whereas Trio GEF2-mediated RhoA activation increases intracellular tension and reinforces Rac1 activation to promote assembly of VE-cadherin junctions and thereby establish the characteristic restrictive endothelial barrier.

SUBMITTER: Kruse K

PROVIDER: S-EPMC6314553 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability.

Kruse Kevin K Lee Quinn S QS Sun Ying Y Klomp Jeff J Yang Xiaoyan X Huang Fei F Sun Mitchell Y MY Zhao Shuangping S Hong Zhigang Z Vogel Stephen M SM Shin Jae-Won JW Leckband Deborah E DE Tai Leon M LM Malik Asrar B AB Komarova Yulia A YA

The Journal of cell biology 20181121 1

Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin (<i>Cdh2</i>) in either endothelial cells or pericyt ...[more]

PMID: 30463880

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Dataset Information

N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability.

Publications

N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability.

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