Regulation of the chemokine receptors CXCR4 and ACKR3 by receptor activity-modifying proteins.

ABSTRACT: The chemokine CXCL12 and its two cognate receptors-CXCR4 and ACKR3-are key players in various homeostatic and pathophysiological processes, including embryonic development, autoimmune diseases, tissue repair, and cancer. Recent reports identified an interaction of CXCR4 and ACKR3 with receptor activity-modifying proteins (RAMPs), and RAMP3 has been shown to facilitate ACKR3's recycling properties. Yet, the functional effects of RAMPs on the CXCL12 signaling axis remain largely elusive. Here, we characterize the effects of RAMPs on CXCR4 and ACKR3 function. We show that, in the absence of a ligand, RAMPs do not affect the cell membrane localization or constitutive internalization of the two receptors. RAMP3 inhibits ligand-stimulated internalization of ACKR3, which retains the receptor at t

SUBMITTER: Pfersdorf F 

PROVIDER: S-EPMC11760809 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature