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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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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. |
format | Online Article Text |
id | pubmed-6314553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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