Just like classical chemokine receptors, atypical chemokine receptors (ACKRs) are seven-transmembrane-helix (7TM) receptors that bind chemokines []. However, they lack the canonical DRYLAIV motif necessary for GPCR coupling to G proteins and induction of classical signalling pathways. Instead, ACKRs internalise their chemokine ligands, which may subsequently affect chemokine availability. The ACKR family comprises five members: Duffy Antigen Receptor for Chemokines (DARC, ACKR1), D6 (ACKR2), CXCR7 (ACKR3), CCRL1 (ACKR4) and CCRL2 (ACKR5) [].Atypical chemokine receptor 3 (ACKR3), previously known as CXC chemokine receptor 7 (CXCR7), is regarded as a scavenger for CXCL12 and, to a lesser extent, for CXCL11 []. Unlike other CXC chemokine receptors, ACKR3 does not elicit classical chemokine receptor signalling via typical G protein-mediated pathways [], but instead induces beta-arrestin recruitment, leading to ligand internalisation and activation of MAPK signaling pathway [, ].ACKR3/CXCR7 has been identified on memory B cells and in mammals is found in bone, brain, heart and kidney [, ]. It has been shown to act as a novel coreceptor for several immunodeficiency virus strains, which infect brain-derived cells []. Studies in zebrafish have also revealed a critical role in vascular formation and angiogenesis during development []. ACKR3/CXCR7 is a functional receptor for CXCL12 in astrocytomas/glioblastomas and mediates resistance to drug-induced apoptosis []. It has been shown to promote growth of tumors formed from breast and lung cancer cells [].
