β-Arrestin-Dependent Activation of the Cofilin Pathway Is Required for the Scavenging Activity of the Atypical Chemokine Receptor D6
| Autor: | Françoise Bachelerie, Cinzia Cancellieri, Raffaella Bonecchi, Yann Benureau, Bernard Lagane, Alberto Mantovani, Elena Monica Borroni, Alessandro Vacchini, Fernando Arenzana-Seisdedos, Kensaku Mizuno, Massimo Locati |
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| Přispěvatelé: | Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano = University of Milan (UNIMI), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Pathogénie Virale, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomolecular Sciences, Tohoku University [Sendai], This study was supported by research grants from the European Community's Seventh Framework Programme (FP7-2007-2013) under grant agreement HEALTH-F4-2011-281608 (TIMER), Ministero dell'Istruzione dell'Università e della Ricerca [PRIN projects, Fondo per gli Investimenti della Ricerca di Base (FIRB) projects RBFR08CW8G and RBFR10HP97], Fondazione Humanitas per la Ricerca, and the Italian Association for Cancer Research (AIRC). Y.B. is a recipient of a Union for International Cancer Control Fellowship. Author, University of Milan, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CCR1
rac1 GTP-Binding Protein Arrestins CCR3 C-C chemokine receptor type 6 CHO Cells Receptors CCR10 Biology Biochemistry 03 medical and health sciences Chemokine receptor 0302 clinical medicine Cricetulus Cricetinae Animals Humans CCR10 CXC chemokine receptors Molecular Biology beta-Arrestins 030304 developmental biology G protein-coupled receptor 0303 health sciences Lim Kinases Cell Biology 3. Good health Cell biology Actin Depolymerizing Factors p21-Activated Kinases 030220 oncology & carcinogenesis [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Signal transduction Signal Transduction |
| Zdroj: | Science Signaling Science Signaling, 2013, 6 (273), pp.ra30. ⟨10.1126/scisignal.2003627⟩ Science Signaling, American Association for the Advancement of Science, 2013, 6 (273), pp.ra30. ⟨10.1126/scisignal.2003627⟩ Scopus-Elsevier Science Signaling; Vol 6 |
| ISSN: | 1937-9145 |
| DOI: | 10.1126/scisignal.2003627⟩ |
| Popis: | International audience; Chemokines promote the recruitment of leukocytes to sites of infection and inflammation by activating conventional heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). Chemokines are also recognized by a set of atypical chemokine receptors (ACRs), which cannot induce directional cell migration but are required for the generation of chemokine gradients in tissues. ACRs are presently considered "silent receptors" because no G protein-dependent signaling activity is observed after their engagement by cognate ligands. We report that engagement of the ACR D6 by its ligands activates a β-arrestin1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the Rac1-p21-activated kinase 1 (PAK1)-LIM kinase 1 (LIMK1) cascade. This signaling pathway is required for the increased abundance of D6 protein at the cell surface and for its chemokine-scavenging activity. We conclude that D6 is a signaling receptor that exerts its regulatory function on chemokine-mediated responses in inflammation and immunity through a distinct signaling pathway. |
| Databáze: | OpenAIRE |
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