The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes.
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 approximately 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.
Balabanian
Karl
K
Unité d'Immunologie Virale, Institut Pasteur, 75015 Paris, France.
Lagane
Bernard
B
Infantino
Simona
S
Chow
Ken Y C
KY
Harriague
Julie
J
Moepps
Barbara
B
Arenzana-Seisdedos
Fernando
F
Thelen
Marcus
M
Bachelerie
Françoise
F
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry; D019921:Biotinylation; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000737:chemistry / Q000502:physiology*; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018274:Electroporation; D005434:Flow Cytometry; D005822:Genetic Vectors; D006678:HIV / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D054387:Receptors, CXCR; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology
C501896:ACKR3 protein, human; D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D008024:Ligands; D054387:Receptors, CXCR; D043562:Receptors, G-Protein-Coupled