The Chemokine SDF-1/CXCL12 Binds to and Signals through the Orphan Receptor RDC1 in T Lymphocytes

Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M and Bachelerie F
Source: J Biol Chem
Publication Date: (2005)
Issue: 280(42): 35760-35766
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Fibroblast, dermal(NHDF-Ad), human adult
Species: human
Tissue Origin: dermal
Nucleofector® I/II/2b
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 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. Further, 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.