MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression
Entity
UAM. Departamento de Biología MolecularPublisher
The American Society of Cell BiologyDate
2013-02-15Citation
10.1091/mbc.E11-11-0914
Molecular Biology of the Cell 24.4 (2013): 483-494
ISSN
1059-1524 (print); 1939-4586 (online)DOI
10.1091/mbc.E11-11-0914Funded by
This work was supported by grants SAF2011–22624 (to J.M.), BFU2012–32532 and CSD2009–00016 (to M.A.A.), and BFU2011-22859 (to I.C.) from the Ministerio de Ciencia e Innovación; and grant S2010/BMD-2305 from the Comunidad de Madrid (to I.C.). J.F.A. was the recipient of an EMBO short-term fellowship in A.J.R.’s laboratoryProject
Comunidad de Madrid. S2010/BMD-2305/CS INTERACTOMICSEditor's Version
http://dx.doi.org/10.1091/mbc.E11-11-0914Subjects
Endothelium; MYADM; Biología y Biomedicina / BiologíaNote
This article was published online ahead of print in MBoC in Press (http://www .molbiolcell.org/cgi/doi/10.1091/mbc.E11-11-0914) on December 21, 2012Supplemental Material can be found at: http://www.molbiolcell.org/content/suppl/2012/12/17/mbc.E11-11-0914v1.DC1.html
Rights
© 2013 Aranda et al.Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional.
Abstract
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
Files in this item
Google Scholar:Aranda, Juan F.
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Reglero-Reala, Natalia
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Marcos-Ramiro, Beatriz
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Ruiz-Sáenz, Ana
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Fernández-Martín, Laura
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Bernabé-Rubio, Miguel
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Kremer, Leonor
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Ridley, Anne J.
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Correas Hornero, María Isabel
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Alonso, Miguel Angel
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Millán, Jaime
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