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MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression
The endothelium maintains a barrier between blood and tissue that becomes more permeable during inflammation. Membrane rafts are ordered assemblies of cholesterol, glycolipids, and proteins that modulate proinflammatory cell signaling and barrier function. In epithelial cells, the MAL family members...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571871/ https://www.ncbi.nlm.nih.gov/pubmed/23264465 http://dx.doi.org/10.1091/mbc.E11-11-0914 |
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author | Aranda, Juan F. Reglero-Real, Natalia Marcos-Ramiro, Beatriz Ruiz-Sáenz, Ana Fernández-Martín, Laura Bernabé-Rubio, Miguel Kremer, Leonor Ridley, Anne J. Correas, Isabel Alonso, Miguel A. Millán, Jaime |
author_facet | Aranda, Juan F. Reglero-Real, Natalia Marcos-Ramiro, Beatriz Ruiz-Sáenz, Ana Fernández-Martín, Laura Bernabé-Rubio, Miguel Kremer, Leonor Ridley, Anne J. Correas, Isabel Alonso, Miguel A. Millán, Jaime |
author_sort | Aranda, Juan F. |
collection | PubMed |
description | The endothelium maintains a barrier between blood and tissue that becomes more permeable during inflammation. Membrane rafts are ordered assemblies of cholesterol, glycolipids, and proteins that modulate proinflammatory cell signaling and barrier function. In epithelial cells, the MAL family members MAL, MAL2, and myeloid-associated differentiation marker (MYADM) regulate the function and dynamics of ordered membrane domains. We analyzed the expression of these three proteins in human endothelial cells and found that only MYADM is expressed. MYADM was confined in ordered domains at the plasma membrane, where it partially colocalized with filamentous actin and cell–cell junctions. Small interfering RNA (siRNA)-mediated MYADM knockdown increased permeability, ICAM-1 expression, and leukocyte adhesion, all of which are features of an inflammatory response. Barrier function decrease in MYADM-silenced cells was dependent on ICAM-1 expression. Membrane domains and the underlying actin cytoskeleton can regulate each other and are connected by ezrin, radixin, and moesin (ERM) proteins. In endothelial cells, MYADM knockdown induced ERM activation. Triple-ERM knockdown partially inhibited ICAM-1 increase induced by MYADM siRNA. Importantly, ERM knockdown also reduced ICAM-1 expression in response to the proinflammatory cytokine tumor necrosis factor-α. MYADM therefore regulates the connection between the plasma membrane and the cortical cytoskeleton and so can control the endothelial inflammatory response. |
format | Online Article Text |
id | pubmed-3571871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35718712013-04-30 MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression Aranda, Juan F. Reglero-Real, Natalia Marcos-Ramiro, Beatriz Ruiz-Sáenz, Ana Fernández-Martín, Laura Bernabé-Rubio, Miguel Kremer, Leonor Ridley, Anne J. Correas, Isabel Alonso, Miguel A. Millán, Jaime Mol Biol Cell Articles The endothelium maintains a barrier between blood and tissue that becomes more permeable during inflammation. Membrane rafts are ordered assemblies of cholesterol, glycolipids, and proteins that modulate proinflammatory cell signaling and barrier function. In epithelial cells, the MAL family members MAL, MAL2, and myeloid-associated differentiation marker (MYADM) regulate the function and dynamics of ordered membrane domains. We analyzed the expression of these three proteins in human endothelial cells and found that only MYADM is expressed. MYADM was confined in ordered domains at the plasma membrane, where it partially colocalized with filamentous actin and cell–cell junctions. Small interfering RNA (siRNA)-mediated MYADM knockdown increased permeability, ICAM-1 expression, and leukocyte adhesion, all of which are features of an inflammatory response. Barrier function decrease in MYADM-silenced cells was dependent on ICAM-1 expression. Membrane domains and the underlying actin cytoskeleton can regulate each other and are connected by ezrin, radixin, and moesin (ERM) proteins. In endothelial cells, MYADM knockdown induced ERM activation. Triple-ERM knockdown partially inhibited ICAM-1 increase induced by MYADM siRNA. Importantly, ERM knockdown also reduced ICAM-1 expression in response to the proinflammatory cytokine tumor necrosis factor-α. MYADM therefore regulates the connection between the plasma membrane and the cortical cytoskeleton and so can control the endothelial inflammatory response. The American Society for Cell Biology 2013-02-15 /pmc/articles/PMC3571871/ /pubmed/23264465 http://dx.doi.org/10.1091/mbc.E11-11-0914 Text en © 2013 Aranda 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 BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Aranda, Juan F. Reglero-Real, Natalia Marcos-Ramiro, Beatriz Ruiz-Sáenz, Ana Fernández-Martín, Laura Bernabé-Rubio, Miguel Kremer, Leonor Ridley, Anne J. Correas, Isabel Alonso, Miguel A. Millán, Jaime MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title | MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title_full | MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title_fullStr | MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title_full_unstemmed | MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title_short | MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression |
title_sort | myadm controls endothelial barrier function through erm-dependent regulation of icam-1 expression |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571871/ https://www.ncbi.nlm.nih.gov/pubmed/23264465 http://dx.doi.org/10.1091/mbc.E11-11-0914 |
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