Title: EBI2 regulates CXCL13‐mediated responses by heterodimerization with CXCR5
Abstract: The FASEB JournalVolume 26, Issue 12 p. 4841-4854 Research CommunicationFree to Read EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5 Rubén Barroso, Rubén Barroso Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorLaura Martínez Muñoz, Laura Martínez Muñoz Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorSergio Barrondo, Sergio Barrondo Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country [Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)], Vitoria-Gasteiz, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, SpainSearch for more papers by this authorBeatriz Vega, Beatriz Vega Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorBorja L. Holgado, Borja L. Holgado Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorPilar Lucas, Pilar Lucas Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorAmparo Baíllo, Amparo Baíllo Department of Mathematics, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorJoan Sallés, Joan Sallés Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country [Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)], Vitoria-Gasteiz, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, SpainSearch for more papers by this authorJosé M. Rodríguez-Frade, José M. Rodríguez-Frade Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorMario Mellado, Corresponding Author Mario Mellado [email protected] Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainCorrespondence: Department of Immunology and Oncology, CNB/CSIC, Darwin 3, Cantoblanco, E-28049 Madrid, Spain. E-mail: [email protected] for more papers by this author Rubén Barroso, Rubén Barroso Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorLaura Martínez Muñoz, Laura Martínez Muñoz Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorSergio Barrondo, Sergio Barrondo Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country [Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)], Vitoria-Gasteiz, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, SpainSearch for more papers by this authorBeatriz Vega, Beatriz Vega Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorBorja L. Holgado, Borja L. Holgado Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorPilar Lucas, Pilar Lucas Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorAmparo Baíllo, Amparo Baíllo Department of Mathematics, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorJoan Sallés, Joan Sallés Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country [Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)], Vitoria-Gasteiz, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, SpainSearch for more papers by this authorJosé M. Rodríguez-Frade, José M. Rodríguez-Frade Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainSearch for more papers by this authorMario Mellado, Corresponding Author Mario Mellado [email protected] Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, SpainCorrespondence: Department of Immunology and Oncology, CNB/CSIC, Darwin 3, Cantoblanco, E-28049 Madrid, Spain. E-mail: [email protected] for more papers by this author First published: 22 August 2012 https://doi.org/10.1096/fj.12-208876Citations: 9 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract B-cell movement into lymphoid follicles depends on the expression of the chemokine receptor CXCR5 and the recently reported Epstein-Barr virus-induced receptor 2 (EBI2). In cooperation with CXCR5, EBI2 helps to position activated B cells in the follicle, although the mechanism is poorly understood. Using human HEK293T cells and fluorescence resonance energy transfer (FRET) techniques, we demonstrate that CXCR5 and EBI2 form homo- and heterodimers. EBI2 expression modulated CXCR5 homodimeric complexes, as indicated by the FRET50 value (CXCR5 homodimer, 0.9851±0.0784; CXCR5 homodimer+EBI2, 1.7320±0.4905; P<0.05). HEK293T cells expressing CXCR5/EBI2 and primary activated murine B cells both down-modulated CXCR5-mediated responses, such as Ca2+ flux, cell migration, and MAPK activation; this modulation did not occur when primary B cells were obtained from EBI2–/– mice. The mechanism involves a reduction in binding affinity of the ligand (CXCL13) for CXCR5 (KD: 5.05×10–8 M for CXCR5 alone vs. 1.49×10–7 M for CXCR5/EBI2) and in the efficacy (Emax) of G-protein activation in CXCR5/EBI2-coexpressing cells (42.33±4.3%; P<0.05). These findings identify CXCR5/EBI2 heterodimers as functional units that contribute to the plasticity of CXCL13-mediated B-cell responses.—Barroso, R., Muñoz, L. Martínez., Barrondo, S., Vega, B., Holgado, B. L., Lucas, P., Baíllo, A., Sallés, J., Rodríguez-Frade J. M., Mellado, M. EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5. FASEB J. 26, 4841–4854 (2012). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2026012008-sup-0001.zipZip archive, 1.5 MB Supplementary material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume26, Issue12December 2012Pages 4841-4854 RelatedInformation
Publication Year: 2012
Publication Date: 2012-08-22
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 40
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