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J. Biol. Chem., Vol. 280, Issue 42, 35760-35766, October 21, 2005
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The Chemokine SDF-1/CXCL12 Binds to and Signals through the Orphan Receptor RDC1 in T Lymphocytes*
1213
435
From the
Unité d'Immunologie Virale, Institut Pasteur, 75015 Paris, France, the Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland, and the ¶Department of Pharmacology and Toxicology, University of Ulm, D-89081 Ulm, Germany
Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD 
0.4 nM). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.
Received for publication, July 27, 2005 , and in revised form, August 11, 2005.
* This work was supported by Ensemble Contre le SIDA (SIDACTION), INSERM, the Agence Nationale contre le SIDA (ANRS), the Helmut Horten Foundation, and the Swiss National Science Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Both of these authors contributed equally to this work.
2 Supported by a Young Investigator Fellowship from INSERM.
3 Supported by fellowships from SIDACTION and ANRS.
4 Supported by a scholarship from the Croucher Foundation (Hong Kong).
5 To whom correspondence should be addressed: Unité d'Immunologie Virale, Inst. Pasteur, 28 Rue du Dr. Roux, 75015 Paris, France. Tel.: 33-1-40613467; Fax: 33-1-45688941; E-mail: fbachele{at}pasteur.fr.
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