MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression

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dc.contributor.author Aranda, Juan F.
dc.contributor.author Reglero-Reala, Natalia
dc.contributor.author Marcos-Ramiro, Beatriz
dc.contributor.author Ruiz-Sáenz, Ana
dc.contributor.author Fernández-Martín, Laura
dc.contributor.author Bernabé-Rubio, Miguel
dc.contributor.author Kremer, Leonor
dc.contributor.author Ridley, Anne J.
dc.contributor.author Correas, Isabel
dc.contributor.author Alonso, Miguel A.
dc.contributor.author Millán, Jaime
dc.contributor.other UAM. Departamento de Biología Molecular es_ES
dc.date.accessioned 2015-07-08T11:56:10Z
dc.date.available 2015-07-08T11:56:10Z
dc.date.issued 2013-02-15
dc.identifier.citation Molecular Biology of the Cell 24.4 (2013): 483-494 es_ES
dc.identifier.issn 1059-1524 (print) en_US
dc.identifier.issn 1939-4586 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/667302
dc.description 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, 2012 en_US
dc.description Supplemental Material can be found at: http://www.molbiolcell.org/content/suppl/2012/12/17/mbc.E11-11-0914v1.DC1.html en_US
dc.description.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 en_US
dc.description.sponsorship 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 laboratory en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng es_ES
dc.publisher The American Society of Cell Biology en_US
dc.relation.ispartof Molecular Biology of the Cell en_US
dc.rights © 2013 Aranda et al. es_ES
dc.subject.other Endothelium en_US
dc.subject.other MYADM en_US
dc.title MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression en_US
dc.type article en
dc.subject.eciencia Biología y Biomedicina / Biología es_ES
dc.relation.publisherversion http://dx.doi.org/10.1091/mbc.E11-11-0914 es_ES
dc.identifier.doi 10.1091/mbc.E11-11-0914 es_ES
dc.identifier.publicationfirstpage 483 es_ES
dc.identifier.publicationissue 4 es_ES
dc.identifier.publicationlastpage 494 es_ES
dc.identifier.publicationvolume 24 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2305/CS INTERACTOMICS es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento – NoComercial – CompartirIgual es_ES
dc.rights.accessRights openAccess es_ES
dc.authorUAM Correas Hornero, María Isabel (260150)


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