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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6085-6093. Prepublished online as a Blood First Edition Paper on April 20, 2009; DOI 10.1182/blood-2008-12-196618. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-12-196618v1 113/24/6085    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Levoye, A. Articles by Lagane, B. PubMed PubMed Citation Articles by Levoye, A. Articles by Lagane, B. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling Angélique Levoye1,2, Karl Balabanian1,2, Françoise Baleux3, Françoise Bachelerie1,2, and Bernard Lagane1,2 1 Inserm U819, Paris; and 2 Unité de Pathogénie Virale, Département de Virologie, and 3 Unité de Chimie Organique, Institut Pasteur, Paris, France The stromal cell-derived factor-1/CXCL12 chemokine engages the CXCR4 and CXCR7 receptors and regulates homeostatic and pathologic processes, including organogenesis, leukocyte homeostasis, and tumorigenesis. Both receptors are widely expressed in mammalian cells, but how they cooperate to respond to CXCL12 is not well understood. Here, we show that CXCR7 per se does not trigger Gi protein–dependent signaling, although energy transfer assays indicate that it constitutively interacts with Gi proteins and undergoes CXCL12-mediated conformational changes. Moreover, when CXCR4 and CXCR7 are coexpressed, we show that receptor heterodimers form as efficiently as receptor homodimers, thus opening the possibility that CXCR4/CXCR7 heterodimer formation has consequences on CXCL12-mediated signals. Indeed, expression of CXCR7 induces conformational rearrangements within preassembled CXCR4/Gi protein complexes and impairs CXCR4-promoted Gi-protein activation and calcium responses. Varying CXCR7 expression levels and blocking CXCL12/CXCR7 interactions in primary T cells suggest that CXCR4/CXCR7 heterodimers form in primary lymphocytes and regulate CXCL12-promoted chemotaxis. Taken together, these results identify CXCR4/CXCR7 heterodimers as distinct functional units with novel properties, which can contribute to the functional plasticity of CXCL12. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. A. Zabel, Y. Wang, S. Lewen, R. D. Berahovich, M. E. T. Penfold, P. Zhang, J. Powers, B. C. Summers, Z. Miao, B. Zhao, et al. Elucidation of CXCR7-Mediated Signaling Events and Inhibition of CXCR4-Mediated Tumor Cell Transendothelial Migration by CXCR7 Ligands J. Immunol., September 1, 2009; 183(5): 3204 - 3211. [Abstract] [Full Text] [PDF]

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