title: Filamin a binds to CCR2B and regulates its internalization.
abstract: The chemokine (C-C motif) receptor 2B (CCR2B) is one of the two isoforms of the receptor for monocyte chemoattractant protein-1 (CCL2), the major chemoattractant for monocytes, involved in an array of chronic inflammatory diseases. Employing the yeast two-hybrid system, we identified the actin-binding protein filamin A (FLNa) as a protein that associates with the carboxyl-terminal tail of CCR2B. Co-immunoprecipitation experiments and in vitro pull down assays demonstrated that FLNa binds constitutively to CCR2B. The colocalization of endogenous CCR2B and filamin A was detected at the surface and in internalized vesicles of THP-1 cells. In addition, CCR2B and FLNa were colocalized in lamellipodia structures of CCR2B-expressing A7 cells. Expression of the receptor in filamin-deficient M2 cells together with siRNA experiments knocking down FLNa in HEK293 cells, demonstrated that lack of FLNa delays the internalization of the receptor. Furthermore, depletion of FLNa in THP-1 monocytes by RNA interference reduced the migration of cells in response to MCP-1. Therefore, FLNa emerges as an important protein for controlling the internalization and spatial localization of the CCR2B receptor in different dynamic membrane structures.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Laura
authors.initials: L
authors.lastname: Minsaas
authors.forename: Jesús
authors.initials: J
authors.lastname: Planagumà
authors.forename: Michael
authors.initials: M
authors.lastname: Madziva
authors.forename: Beate F
authors.initials: BF
authors.lastname: Krakstad
authors.forename: Míriam
authors.initials: M
authors.lastname: Masià-Balagué
authors.forename: Arieh A
authors.initials: AA
authors.lastname: Katz
authors.forename: Anna M
authors.initials: AM
authors.lastname: Aragay
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000494:pharmacology; D003285:Contractile Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D054390:Receptors, CCR2 / Q000737:chemistry / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: D000199:Actins; D019390:Arrestins; D018932:Chemokine CCL2; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D054390:Receptors, CCR2; D000071557:beta-Arrestins
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