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ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation
Intercellular junctions are crucial for mechanotransduction, but whether tight junctions contribute to the regulation of cell–cell tension and adherens junctions is unknown. Here, we demonstrate that the tight junction protein ZO-1 regulates tension acting on VE-cadherin–based adherens junctions, ce...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362456/ https://www.ncbi.nlm.nih.gov/pubmed/25753039 http://dx.doi.org/10.1083/jcb.201404140 |
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author | Tornavaca, Olga Chia, Minghao Dufton, Neil Almagro, Lourdes Osuna Conway, Daniel E. Randi, Anna M. Schwartz, Martin A. Matter, Karl Balda, Maria S. |
author_facet | Tornavaca, Olga Chia, Minghao Dufton, Neil Almagro, Lourdes Osuna Conway, Daniel E. Randi, Anna M. Schwartz, Martin A. Matter, Karl Balda, Maria S. |
author_sort | Tornavaca, Olga |
collection | PubMed |
description | Intercellular junctions are crucial for mechanotransduction, but whether tight junctions contribute to the regulation of cell–cell tension and adherens junctions is unknown. Here, we demonstrate that the tight junction protein ZO-1 regulates tension acting on VE-cadherin–based adherens junctions, cell migration, and barrier formation of primary endothelial cells, as well as angiogenesis in vitro and in vivo. ZO-1 depletion led to tight junction disruption, redistribution of active myosin II from junctions to stress fibers, reduced tension on VE-cadherin and loss of junctional mechanotransducers such as vinculin and PAK2, and induced vinculin dissociation from the α-catenin–VE-cadherin complex. Claudin-5 depletion only mimicked ZO-1 effects on barrier formation, whereas the effects on mechanotransducers were rescued by inhibition of ROCK and phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation. ZO-1 was required for junctional recruitment of JACOP, which, in turn, recruited p114RhoGEF. ZO-1 is thus a central regulator of VE-cadherin–dependent endothelial junctions that orchestrates the spatial actomyosin organization, tuning cell–cell tension, migration, angiogenesis, and barrier formation. |
format | Online Article Text |
id | pubmed-4362456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43624562015-09-16 ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation Tornavaca, Olga Chia, Minghao Dufton, Neil Almagro, Lourdes Osuna Conway, Daniel E. Randi, Anna M. Schwartz, Martin A. Matter, Karl Balda, Maria S. J Cell Biol Research Articles Intercellular junctions are crucial for mechanotransduction, but whether tight junctions contribute to the regulation of cell–cell tension and adherens junctions is unknown. Here, we demonstrate that the tight junction protein ZO-1 regulates tension acting on VE-cadherin–based adherens junctions, cell migration, and barrier formation of primary endothelial cells, as well as angiogenesis in vitro and in vivo. ZO-1 depletion led to tight junction disruption, redistribution of active myosin II from junctions to stress fibers, reduced tension on VE-cadherin and loss of junctional mechanotransducers such as vinculin and PAK2, and induced vinculin dissociation from the α-catenin–VE-cadherin complex. Claudin-5 depletion only mimicked ZO-1 effects on barrier formation, whereas the effects on mechanotransducers were rescued by inhibition of ROCK and phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation. ZO-1 was required for junctional recruitment of JACOP, which, in turn, recruited p114RhoGEF. ZO-1 is thus a central regulator of VE-cadherin–dependent endothelial junctions that orchestrates the spatial actomyosin organization, tuning cell–cell tension, migration, angiogenesis, and barrier formation. The Rockefeller University Press 2015-03-16 /pmc/articles/PMC4362456/ /pubmed/25753039 http://dx.doi.org/10.1083/jcb.201404140 Text en © 2015 Tornavaca et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Tornavaca, Olga Chia, Minghao Dufton, Neil Almagro, Lourdes Osuna Conway, Daniel E. Randi, Anna M. Schwartz, Martin A. Matter, Karl Balda, Maria S. ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title | ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title_full | ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title_fullStr | ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title_full_unstemmed | ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title_short | ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
title_sort | zo-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362456/ https://www.ncbi.nlm.nih.gov/pubmed/25753039 http://dx.doi.org/10.1083/jcb.201404140 |
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