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ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity
Maintenance and remodeling of endothelial cell junctions critically depend on the VE-cadherin/catenin complex and its interaction with the actin filament cytoskeleton. Here we demonstrate that local lack of vascular endothelial (VE)-cadherin at established cell junctions causes actin-driven and acti...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890345/ https://www.ncbi.nlm.nih.gov/pubmed/24227887 http://dx.doi.org/10.1091/mbc.E13-07-0404 |
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author | Taha, Abdallah Abu Taha, Muna Seebach, Jochen Schnittler, Hans-J. |
author_facet | Taha, Abdallah Abu Taha, Muna Seebach, Jochen Schnittler, Hans-J. |
author_sort | Taha, Abdallah Abu |
collection | PubMed |
description | Maintenance and remodeling of endothelial cell junctions critically depend on the VE-cadherin/catenin complex and its interaction with the actin filament cytoskeleton. Here we demonstrate that local lack of vascular endothelial (VE)-cadherin at established cell junctions causes actin-driven and actin-related protein 2/3 complex (ARP2/3)–controlled lamellipodia to appear intermittently at those sites. Lamellipodia overlap the VE-cadherin–free adjacent plasma membranes and facilitate formation of new VE-cadherin adhesion sites, which quickly move into the junctions, driving VE-cadherin dynamics and remodeling. Inhibition of the ARP2/3 complex by expression of the N-WASP (V)CA domain or application of two ARP2/3 inhibitors, CK-548 and CK-666, blocks VE-cadherin dynamics and causes intercellular gaps. Furthermore, expression of carboxy-terminal–truncated VE-cadherin increases the number of ARP2/3-controlled lamellipodia, whereas overexpression of wild-type VE-cadherin largely blocks it and decreases cell motility. The data demonstrate a functional interrelationship between VE-cadherin–mediated cell adhesion and actin-driven, ARP2/3-controlled formation of new VE-cadherin adhesion sites via intermittently appearing lamellipodia at established cell junctions. This coordinated mechanism controls VE-cadherin dynamics and cell motility and maintains monolayer integrity, thus potentially being relevant in disease and angiogenesis. |
format | Online Article Text |
id | pubmed-3890345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38903452014-03-30 ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity Taha, Abdallah Abu Taha, Muna Seebach, Jochen Schnittler, Hans-J. Mol Biol Cell Articles Maintenance and remodeling of endothelial cell junctions critically depend on the VE-cadherin/catenin complex and its interaction with the actin filament cytoskeleton. Here we demonstrate that local lack of vascular endothelial (VE)-cadherin at established cell junctions causes actin-driven and actin-related protein 2/3 complex (ARP2/3)–controlled lamellipodia to appear intermittently at those sites. Lamellipodia overlap the VE-cadherin–free adjacent plasma membranes and facilitate formation of new VE-cadherin adhesion sites, which quickly move into the junctions, driving VE-cadherin dynamics and remodeling. Inhibition of the ARP2/3 complex by expression of the N-WASP (V)CA domain or application of two ARP2/3 inhibitors, CK-548 and CK-666, blocks VE-cadherin dynamics and causes intercellular gaps. Furthermore, expression of carboxy-terminal–truncated VE-cadherin increases the number of ARP2/3-controlled lamellipodia, whereas overexpression of wild-type VE-cadherin largely blocks it and decreases cell motility. The data demonstrate a functional interrelationship between VE-cadherin–mediated cell adhesion and actin-driven, ARP2/3-controlled formation of new VE-cadherin adhesion sites via intermittently appearing lamellipodia at established cell junctions. This coordinated mechanism controls VE-cadherin dynamics and cell motility and maintains monolayer integrity, thus potentially being relevant in disease and angiogenesis. The American Society for Cell Biology 2014-01-15 /pmc/articles/PMC3890345/ /pubmed/24227887 http://dx.doi.org/10.1091/mbc.E13-07-0404 Text en © 2014 Taha et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Taha, Abdallah Abu Taha, Muna Seebach, Jochen Schnittler, Hans-J. ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title | ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title_full | ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title_fullStr | ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title_full_unstemmed | ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title_short | ARP2/3-mediated junction-associated lamellipodia control VE-cadherin–based cell junction dynamics and maintain monolayer integrity |
title_sort | arp2/3-mediated junction-associated lamellipodia control ve-cadherin–based cell junction dynamics and maintain monolayer integrity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890345/ https://www.ncbi.nlm.nih.gov/pubmed/24227887 http://dx.doi.org/10.1091/mbc.E13-07-0404 |
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