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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...

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Autores principales: Taha, Abdallah Abu, Taha, Muna, Seebach, Jochen, Schnittler, Hans-J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
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.
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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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