The biochemistry and biology of the atypical chemokine receptors

A subset of chemokine receptors, initially called “silent” on the basis of their apparent failure to activate conventional signalling events, has recently attracted growing interest due to their ability to internalize, degrade, or transport ligands and thus modify gradients and create functional chemokine patterns in tissues. These receptors recognize distinct and complementary sets of ligands with high affinity, are strategically expressed in different cellular contexts, and lack structural determinants supporting Gαi activation, a key signalling event in cell migration. This is in keeping with the hypothesis that they have evolved to fulfil fundamentally different functions to the classical signalling chemokine receptors. Based on these considerations, these receptors (D6, Duffy antigen receptor for chemokines (DARC), CCX-CKR1 and CXCR7) are now collectively considered as an emerging class of ‘atypical’ chemokine receptors. In this article, we review the biochemistry and biology of this emerging chemokine receptor subfamily.

► This review discusses the members of the ‘atypical’ chemokine receptor family.
► Atypical chemokine receptors have evolved to perform distinct functions.
► Atypical chemokine receptors display an apparent lack of signalling ability.
► Atypical receptors can scavenge chemokines to create functional patterns in tissues.
► Biology, biochemistry and relevance to human health of the receptors is described.