Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling.

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_B9D8C8D01BAB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling.
Périodique
Journal of Cell Science
Auteur(s)
Pons M., Izquierdo I., Andreu-Carbó M., Garrido G., Planagumà J., Muriel O., Del Pozo M.A., Geli M.I., Aragay A.M.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
130
Numéro
2
Pages
490-501
Langue
anglais
Résumé
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.

Mots-clé
GPCR, CCR2, Filamin A, Recycling
Pubmed
Web of science
Création de la notice
03/04/2017 14:11
Dernière modification de la notice
03/03/2018 20:52
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