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

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...

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Autores principales: Kruse, Kevin, Lee, Quinn S., Sun, Ying, Klomp, Jeff, Yang, Xiaoyan, Huang, Fei, Sun, Mitchell Y., Zhao, Shuangping, Hong, Zhigang, Vogel, Stephen M., Shin, Jae-Won, Leckband, Deborah E., Tai, Leon M., Malik, Asrar B., Komarova, Yulia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314553/
https://www.ncbi.nlm.nih.gov/pubmed/30463880
http://dx.doi.org/10.1083/jcb.201802076
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author Kruse, Kevin
Lee, Quinn S.
Sun, Ying
Klomp, Jeff
Yang, Xiaoyan
Huang, Fei
Sun, Mitchell Y.
Zhao, Shuangping
Hong, Zhigang
Vogel, Stephen M.
Shin, Jae-Won
Leckband, Deborah E.
Tai, Leon M.
Malik, Asrar B.
Komarova, Yulia A.
author_facet Kruse, Kevin
Lee, Quinn S.
Sun, Ying
Klomp, Jeff
Yang, Xiaoyan
Huang, Fei
Sun, Mitchell Y.
Zhao, Shuangping
Hong, Zhigang
Vogel, Stephen M.
Shin, Jae-Won
Leckband, Deborah E.
Tai, Leon M.
Malik, Asrar B.
Komarova, Yulia A.
author_sort Kruse, Kevin
collection PubMed
description 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.
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spelling pubmed-63145532019-07-07 N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability Kruse, Kevin Lee, Quinn S. Sun, Ying Klomp, Jeff Yang, Xiaoyan Huang, Fei Sun, Mitchell Y. Zhao, Shuangping Hong, Zhigang Vogel, Stephen M. Shin, Jae-Won Leckband, Deborah E. Tai, Leon M. Malik, Asrar B. Komarova, Yulia A. J Cell Biol Research Articles 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. Rockefeller University Press 2019-01-07 /pmc/articles/PMC6314553/ /pubmed/30463880 http://dx.doi.org/10.1083/jcb.201802076 Text en © 2018 Kruse et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kruse, Kevin
Lee, Quinn S.
Sun, Ying
Klomp, Jeff
Yang, Xiaoyan
Huang, Fei
Sun, Mitchell Y.
Zhao, Shuangping
Hong, Zhigang
Vogel, Stephen M.
Shin, Jae-Won
Leckband, Deborah E.
Tai, Leon M.
Malik, Asrar B.
Komarova, Yulia A.
N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title_full N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title_fullStr N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title_full_unstemmed N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title_short N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability
title_sort n-cadherin signaling via trio assembles adherens junctions to restrict endothelial permeability
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314553/
https://www.ncbi.nlm.nih.gov/pubmed/30463880
http://dx.doi.org/10.1083/jcb.201802076
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