ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function.

ABSTRACT:

Background

Platelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardiovascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signalling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function.

Methods and results

Using a proximity ligation assay (PLA, Duolink®) to screen for CXCR4/ACKR3 heterodimerization inducing compounds,

SUBMITTER: Dicenta-Baunach V 

PROVIDER: S-EPMC11628653 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature