Disease relevance of CXCR7

• 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 [1].
• These findings indicate that RDC1 is a novel coreceptor for several HIV-1, HIV-2, and SIV strains which infect brain-derived cells [2].
• A putative G protein-coupled receptor, RDC1, is a novel coreceptor for human and simian immunodeficiency viruses [2].
• Fusion of RDC1 with HMGA2 in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15 [3].
• Treatment for 24h with RDC1 agonist led to altered expression of a number of genes associated with chondrocyte hypertrophy and increased matrix degradation in human primary chondrocytes, and elevated total matrix metalloproteinase (MMP) activity in cartilage explant [4].
• Immunohistochemistry of primary human tumor tissue demonstrates extensive CXCR7 expression in human breast and lung cancers, where it is highly expressed on a majority of tumor-associated blood vessels and malignant cells but not expressed on normal vasculature [5].
• Together, these data demonstrate a role for CXCR7/RDC1 in PCa metastasis and progression and suggest potential targets for therapeutic intervention [6].

High impact information on CXCR7

• RDC1 may not be VIP receptor [7].
• We indeed report that CpG-activated plasmacytoid DC produce a putative ligand for RDC1, which selectively down-regulates RDC1, but not CXCR4 on primary human B cells [8].
• Based on phylogenetic analysis and chromosomal mapping, the orphan receptor RDC1 was proposed to be a chemokine receptor [8].
• In blood-derived switch memory B cells, the expression of RDC1 appeared to correlate with the ability to differentiate into plasma cells upon activation, suggesting that RDC1 is a marker for memory B cells, which are competent to become Ab-secreting cells [8].
• In this study we examined the expression of RDC1 on leukocytes by measuring mRNA levels and receptor expression using a new specific mAb [8].

Biological context of CXCR7

• We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody [1].
• Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data [9].
• The breakpoint within RDC1 was localized in a previously uncharacterized exon of the gene, and our data suggest that RDC1 is subject to alternative splicing [3].
• In this study, we have characterized a recurrent fusion of the first three exons of HMGA2 5' to the G protein-coupled receptor gene (RDC1) in lipomas with rearrangements involving chromosome bands 2q35-37 and 12q13-15, one of several recurrent chromosomal rearrangements in lipomas [3].

Anatomical context of CXCR7

• The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes [1].
• RDC1 expression was found to be tightly regulated during B cell development and differentiation [8].
• When a CD4-expressing cell line, NP-2/CD4, which shows strict resistance to infection not only with HIV-1 but also with HIV-2 or SIV, was transduced with the RDC1 gene, the cells became highly susceptible to HIV-2 and SIV(mnd) strains but to neither M- nor T-tropic HIV-1 strains [2].
• Treatment of human primary chondrocytes with RDC1 agonist induced a Ca2+ response, suggesting the receptor is active in this tissue type [4].

Other interactions of CXCR7

• Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM) [1].
• The results indicate that human RDC1, RDC4, RDC7, and RDC8 are in regions 2q37, 1p34.3-1p36.3, 22q11.2-22q13.1, and 11q11-11q13, respectively [10].
• Characterization of the G-protein linked orphan receptor GPRN1/RDC1 [11].

Analytical, diagnostic and therapeutic context of CXCR7

• The effect of RDC1 activation on human chondrocytes and cartilage explant gene expression was determined by quantitative real-time polymerase chain reaction (PCR), and these effects validated as being mediated by RDC1 using siRNA antisense [4].

References