Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling

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• dc.contributor.author Pons, Mónicaca
• dc.contributor.author Izquierdo, Ismaelca
• dc.contributor.author Andreu-Carbó, Mireiaca
• dc.contributor.author Garrido, Georginaca
• dc.contributor.author Planagumà, Jesúsca
• dc.contributor.author Muriel, Oliviaca
• dc.contributor.author Pozo, Miguel Ángel delca
• dc.contributor.author Isabel Geli, M.ca
• dc.contributor.author Aragay, Anna M.ca
• dc.date.accessioned 2018-06-15T07:49:54Z
• dc.date.available 2018-06-15T07:49:54Z
• dc.date.issued 2017
• dc.description.abstract Proper endosomal trafficking of ligand-activated G-protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B; one of two isoforms encoded by CCR2), endocytic recycling is important to sustain monocyte migration, whereas filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa-knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates. Utilizing super-resolution microscopy, we observed that FLNa-GFP, CCR2B and β2-adrenergic receptor (β2AR) were present in actin-enriched endosomal microdomains. Depletion of FLNa decreased CCR2B association with these microdomains and concomitantly delayed CCR2B endosomal traffic, without apparently affecting the number of microdomains. Interestingly, CCR2B and β2AR signaling induced phosphorylation of FLNa at residue S2152, and this phosphorylation event was contributes to sustain receptor recycling. Thus, our data strongly suggest that CCR2B and β2AR signals to FLNa to stimulate its endocytosis and recycling to the plasma membrane.
• dc.description.sponsorship This work was supported by grants from Ministerio de Economía y Competitividad (BFU2011-30080 and BFU2014-53978-R); and Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR41635). G.G. and I.I. were supported by Investigator Research Fellowships (Agéncia de Gestió d'Ajuts Universitaris i de Recerca).
• dc.format.mimetype application/pdf
• dc.identifier.citation Pons M, Izquierdo I, Andreu-Carbo M, Garrido G, Planaguma J, Muriel O et al. Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling. J Cell Sci. 2017 Jan 15;130(2):490-501. DOI: 10.1242/jcs.193821. Epub 2016 Dec 1
• dc.identifier.doi http://dx.doi.org/10.1242/jcs.193821
• dc.identifier.issn 0021-9533
• dc.identifier.uri http://hdl.handle.net/10230/34914
• dc.language.iso eng
• dc.publisher Company of Biologistsca
• dc.relation.ispartof J Cell Sci. 2017 Jan 15;130(2):490-501
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-30080
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-53978-R
• dc.rights Published originally by Cold Spring Harbor Laboratory Press at 10.1242/jcs.193821. Beginning six months from the full-issue publication date, articles are distributed under the Creative Commons Attribution-Non-Commercial 4.0 International License (CC-BY-NC), as described at http://creativecommons.org/licenses/by-nc/4.0/. This license permits non-commercial use, including reproduction, adaptation, and distribution of the article provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword G-protein-coupled receptors
• dc.subject.keyword Ccr2
• dc.subject.keyword Filamin A
• dc.subject.keyword Recycling
• dc.title Phosphorylation of filamin A regulates chemokine receptor CCR2 recyclingca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion