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Epithelial protein lost in neoplasm (EPLIN) interacts with α-catenin and actin filaments in endothelial cells and stabilizes vascular capillary network in vitro.: Stabilization of in vitro vascular capillary network by EPLIN

Abstract : Adherens junctions are required for vascular endothelium integrity. These structures are formed by the clustering of the homophilic adhesive protein VE-cadherin, which recruits intracellular partners, such as β- and α-catenins, vinculin, and actin filaments. The dogma according to which α-catenin bridges cadherin*β-catenin complexes to the actin cytoskeleton has been challenged during the past few years, and the link between the VE-cadherin*catenin complex and the actin cytoskeleton remains unclear. Recently, epithelial protein lost in neoplasm (EPLIN) has been proposed as a possible bond between the E-cadherin*catenin complex and actin in epithelial cells. Herein, we show that EPLIN is expressed at similar levels in endothelial and epithelial cells and is located at interendothelial junctions in confluent cells. Co-immunoprecipitation and GST pulldown experiments provided evidence that EPLIN interacts directly with α-catenin and tethers the VE-cadherin*catenin complex to the actin cytoskeleton. In the absence of EPLIN, vinculin was delocalized from the junctions. Furthermore, suppression of actomyosin tension using blebbistatin triggered a similar vinculin delocalization from the junctions. In a Matrigel assay, EPLIN-depleted endothelial cells exhibited a reduced capacity to form pseudocapillary networks because of numerous breakage events. In conclusion, we propose a model in which EPLIN establishes a link between the cadherin*catenin complex and actin that is independent of actomyosin tension. This link acts as a mechanotransmitter, allowing vinculin binding to α-catenin and formation of a secondary molecular bond between the adherens complex and the cytoskeleton through vinculin. In addition, we provide evidence that the EPLIN clutch is necessary for stabilization of capillary structures in an angiogenesis model.
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https://www.hal.inserm.fr/inserm-00763078
Contributor : Nathalie Roux-Buisson <>
Submitted on : Monday, December 10, 2012 - 10:12:14 AM
Last modification on : Thursday, November 19, 2020 - 3:52:09 PM
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CEA | CNRS | U823 | U836 | LTM | URCA | MEDYC | CAPSANTE | UGA

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Adeline Chervin-Pétinot, Marie Courçon, Sébastien Almagro, Alice Nicolas, Alexei Grichine, et al.. Epithelial protein lost in neoplasm (EPLIN) interacts with α-catenin and actin filaments in endothelial cells and stabilizes vascular capillary network in vitro.: Stabilization of in vitro vascular capillary network by EPLIN. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (10), pp.7556-72. ⟨10.1074/jbc.M111.328682⟩. ⟨inserm-00763078⟩

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