Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling.

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State: Public
Version: Final published version
Serval ID
serval:BIB_B9D8C8D01BAB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphorylation of filamin A regulates chemokine receptor CCR2 recycling.
Journal
Journal of Cell Science
Author(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
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
130
Number
2
Pages
490-501
Language
english
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.

Keywords
GPCR, CCR2, Filamin A, Recycling
Pubmed
Web of science
Open Access
Yes
Create date
03/04/2017 13:11
Last modification date
20/08/2019 15:27
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