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dc.contributor.authorMartín-Villar, Ester-
dc.contributor.authorBañón-Rodríguez, Inmaculada-
dc.contributor.authorJones, Gareth E.-
dc.contributor.authorAntón, Inés María-
dc.contributor.authorCalle, Yolanda-
dc.date.accessioned2015-11-02T12:16:05Z-
dc.date.available2015-11-02T12:16:05Z-
dc.date.issued2014-
dc.identifierdoi: 10.1016/j.biocel.2014.01.021-
dc.identifierissn: 1357-2725-
dc.identifiere-issn: 1878-5875-
dc.identifier.citationInternational Journal of Biochemistry and Cell Biology 50: 47-54 (2014)-
dc.identifier.urihttp://hdl.handle.net/10261/124290-
dc.descriptionUnder a Creative Commons license.-- et al.-
dc.description.abstractPodosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and for extracellular matrix (ECM) degradation. We have previously shown that soluble factors and chemokines such as SDF 1-α trigger podosome initiation whereas integrin ligands promote podosome maturation and stability in DCs. The exact intracellular signalling pathways that regulate the sequential organisation of podosomal components in response to extracellular cues remain largely undetermined. The Wiskott Aldrich Syndrome Protein (WASP) mediates actin polymerisation and the initial recruitment of integrins and associated proteins in a circular configuration surrounding the core of filamentous actin (F-actin) during podosome initiation. We have now identified integrin linked kinase (ILK) surrounding the podosomal actin core. We report that DC polarisation in response to chemokines and the assembly of actin cores during podosome initiation require PI3K-dependent clustering of the Wiskott Aldrich Syndrome Protein (WASP) in puncta independently of ILK. ILK is essential for the clustering of integrins and associated proteins leading to podosome maturation and stability that are required for degradation of the subjacent extracellular matrix and the invasive motility of DCs across connective tissue barriers. We conclude that WASP regulates DCs polarisation for migration and initiation of actin polymerisation downstream of PI3K in nascent podosomes. Subsequently, ILK mediates the accumulation of integrin-associated proteins during podosome maturation and stability for efficient degradation of the subjacent ECM during the invasive migration of DCs.-
dc.description.sponsorshipThis work has been supported by grants from the Burton Myeloma Programme (YC), Ministerio Español de Ciencia e Innovación (BFU2010-21374/BMC (IMA)), the Medical Research Council (G1100041, GEJ, IMA) Fundación Científica de la Asociación Española Contra el Cáncer (AECC) (EM-V and IB-R) and the Wellcome Trust (080373) (YC, MPB, AJT and GEJ).-
dc.publisherElsevier-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.titleIntegrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells-
dc.typeartículo-
dc.identifier.doi10.1016/j.biocel.2014.01.021-
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.biocel.2014.01.021-
dc.date.updated2015-11-02T12:16:08Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/3.0/-
dc.contributor.funderMedical Research Council (UK)-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderFundación Científica Asociación Española Contra el Cáncer-
dc.contributor.funderWellcome Trust-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000265es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002704es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100004440es_ES
dc.identifier.pmid24508783-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.grantfulltextopen-
item.openairetypeartículo-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
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