MOL Highlight: Modulation of Chemokine Receptor Function by Cholesterol: New Prospects for Pharmacological Intervention
Chemokine receptors are G-protein-coupled receptors (GPCRs) that play essential roles in directing cell migration, such as during the immune response to bacterial invasion. Recently it has been shown that cholesterol can regulate chemokine receptor function by influencing the spatial organization of these GPCRs within the membrane bilayer as well as tuning chemokine receptor signaling. This review explores a number of ways by which cholesterol and its metabolites are thought to modulate chemokine signaling. The first is to promote chemokine receptor oligomerization, which is posited to create a signaling hub at which multiple signaling pathways can assemble and integrate their activities. The second is to stabilize particular receptor conformations that perturb chemokine binding. Also discussed is how cholesterol accumulation and depletion plays a role in various inflammatory responses, including dampening an anti-tumor immune response.
See the article by Legler et al. at Molecular Pharmacology April 2017, 91 (4) 331-338; DOI: https://doi.org/10.1124/mol.116.107151