CXCR4

CXCR receptors (C-X-C Motif Chemokine Receptors) are a family of chemokine receptors that belong to the group of G-protein-coupled receptors (GPCRs). Chemokine receptors are 7-transmembrane G-protein-coupled receptors that are activated by the binding of one or more chemokines.

CXCR receptors play an essential role in the immune system by influencing the migration of immune cells to sites of inflammation or to tissues. Chemokines are signaling molecules produced by various cells. They form a family of chemoattractive molecules, of which more than 50 have been identified to date. Chemokines are categorized into four main groups according to the number and spacing of conserved cysteines: CXC, CC, CX3C and C. They bind to their specific receptors (e.g. CXCR) and thus initiate a signaling cascade that controls the behavior of immune cells, including their movement, activation and differentiation. In individual cases, this can also influence tumor growth.

CXCR4 (C-X-C Motif Chemokine Receptor 4) is a receptor for the C-X-C chemokine CXCL12/SDF-1. CXCR4 is synonymous with CD184. It is specific for stromal cell factor-1 . The protein receptor is encoded by the gene of the same name(CXCR4 gene), which is located on chromosome 2q22.1. Mutations in the CXCR4 gene are associated with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelocathexis). Waldenstroem macroglobulinemia is also associated with mutations in this gene.

Alternative transcriptional splice variants encoding different isoforms have been characterized. The CXC chemokine receptor (like other chemokine receptors) has 7 transmembrane domains and is located on the cell surface. The receptor interacts with the CD4 protein. The associated activation induces a signal by increasing the intracellular calcium ion level, resulting in an amplification of MAPK1/MAPK3 activation. Plays a role in the regulation of cell migration, e.g. in wound healing.

1. Bachelerie F (2010) CXCL12/CXCR4-axis dysfunctions: Markers of the rare immunodeficiency disorder WHIM syndrome. Dis Markers 29:189-198.
2. Pozzobon T et al. (2016) CXCR4 signaling in health and disease. Immunol Lett 177:6-15.