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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...

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Autores principales: Tornavaca, Olga, Chia, Minghao, Dufton, Neil, Almagro, Lourdes Osuna, Conway, Daniel E., Randi, Anna M., Schwartz, Martin A., Matter, Karl, Balda, Maria S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
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.
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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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