CXCR7

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). There are currently 8 known chemokine receptors. These are 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.

CXCR7 was later renamed ACKR3 (atypical chemokine receptor 3). CXCR7/ACKR3 is a non-classical transmembrane receptor with seven transmembranes whose function as a signaling or non-signaling scavenger/decoy receptor is not fully understood. CXCR7 apparently has > five natural ligands (Wang C et al. 2018) such as SDF-1 (CXCL12), CXCL11(Sánchez-Martín L et al. 2013) and several opioid peptides (Sigmund EC et al. 2023). ACKR3 apparently also binds two other non-chemokine ligands, namely the peptide hormone adrenomedullin (AM) and derivatives of the proadrenomedullin N-terminal 20 peptide (PAMP). AM has several functions in the cardiovascular system and is essential for embryonic lymphangiogenesis in mice. Interestingly, both AM-overexpressing and ACKR3-deficient mouse embryos exhibit lymphoid hyperplasia. Furthermore, in vitro evidence indicated that lymphatic endothelial cells (LECs) expressing ACKR3 scavenge AM and thereby reduce AM-induced lymphangiogenic responses.

1. Khare T et al. (2021) CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies. Int J Mol Sci 22:7371.
2. Sánchez-Martín L et al. (2013) CXCR7 impact on CXCL12 biology and disease. Trends Mol Med 19:12-22.
3. Sigmund EC et al. (2023) Reassessing the adrenomedullin scavenging function of ACKR3 in lymphatic endothelial cells. PLoS One 18:e0285597.
4. Wang C et al. (2018) CXCR7 Targeting and Its Major Disease Relevance. Front Pharmacol 9:641.