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EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5.
MedLine Citation:
PMID:  22913878     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 FRET(50) 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 Ca(2+) 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 (K(D): 5.05×10(-8) M for CXCR5 alone vs. 1.49×10(-7) M for CXCR5/EBI2) and in the efficacy (E(max)) 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. M., 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.
Authors:
Rubén Barroso; Laura Martínez Muñoz; Sergio Barrondo; Beatriz Vega; Borja L Holgado; Pilar Lucas; Amparo Baíllo; Joan Sallés; José M Rodríguez-Frade; Mario Mellado
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-23
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), and.
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