Atypical chemokine receptor 3

Definition:

Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels.; (Microbial infection) Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.

References:

[1]. Ulrike Naumann, et al. CXCR7 functions as a scavenger for CXCL12 and CXCL11. PLoS One. 2010 Feb 11;5(2):e9175. [Content Brief]

[2]. Lorena Sánchez-Martín, et al. CXCR7 impact on CXCL12 biology and disease. Trends Mol Med. 2013 Jan;19(1):12-22. [Content Brief]

[3]. Irina Kalatskaya, et al. AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol Pharmacol. 2009 May;75(5):1240-7. [Content Brief]

[4]. Paramita Ray, et al. Carboxy-terminus of CXCR7 regulates receptor localization and function. Int J Biochem Cell Biol. 2012 Apr;44(4):669-78. [Content Brief]

[5]. Angélique Levoye, et al. CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood. 2009 Jun 11;113(24):6085-93. [Content Brief]

[6]. Mary C Whitman, et al. Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans. Hum Mol Genet. 2019 Sep 15;28(18):3113-3125. [Content Brief]

[7]. Sudarshan Rajagopal, et al. Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):628-32. [Content Brief]

[8]. Karl Balabanian, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem. 2005 Oct 21;280(42):35760-6. [Content Brief]

[9]. Kirsten Hattermann, et al. The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res. 2010 Apr 15;70(8):3299-308. [Content Brief]

[10]. Jennifer M Burns, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006 Sep 4;203(9):2201-13. [Content Brief]

[11]. Brian A Zabel, et al. Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J Immunol. 2009 Sep 1;183(5):3204-11. [Content Brief]

[12]. Frederic Sierro, et al. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14759-64. [Content Brief]

[13]. Maciej Tarnowski, et al. CXCR7: a new SDF-1-binding receptor in contrast to normal CD34(+) progenitors is functional and is expressed at higher level in human malignant hematopoietic cells. Eur J Haematol. 2010 Dec;85(6):472-83. [Content Brief]

[14]. Tanja Nicole Hartmann, et al. A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cells. J Leukoc Biol. 2008 Oct;84(4):1130-40. [Content Brief]

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