Inverse Regulation of C–C Chemokine Receptor 3 Oligomerization by Downstream Proteins Indicates Biased Signal Transduction Pathways

Oligomerization is one of the important mechanisms for G protein-coupled receptors (GPCRs) to modulate their activity in signal transduction. However, details of how and why the oligomerization of GPCRs regulates their functions under physiological conditions remain largely unknown. Here, using single-molecule photobleaching technology, we show that chemokine ligand 5 (CCL5) and chemokine ligand 8 (CCL8) are similar to the previously reported chemokine ligand 11 (CCL11) and chemokine ligand 24 (CCL24), which can regulate the oligomerization of chemokine receptor 3 (CCR3). Our results further demonstrate that downstream proteins, β-arrestin 2 and G