Filamin A Binds to CCR2B and Regulates Its Internalization |
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| Authors: | Laura Minsaas Jesús Planagumà Michael Madziva Beate F Krakstad Míriam Masià-Balagué Arieh A Katz Anna M Aragay |
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| Institution: | 1. Department of Biomedicine, University of Bergen, Bergen, Norway.; 2. Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.; 3. Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.;University of Birmingham, United Kingdom |
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| 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. |
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