Membrane cholesterol depletion enhances ligand binding function of human serotonin<SUB>1A</SUB> receptors in neuronal cells

Membrane lipid composition of cells in the nervous system is unique and displays remarkable diversity. Cholesterol metabolism and homeostasis in the central nervous system and their role in neuronal function represent important determinants in neuropathogenesis. The serotonin1A receptor is an important member of the G-protein coupled receptor superfamily, and is involved in a variety of cognitive, behavioral, and developmental functions. We report here, for the first time, that the ligand binding function of human serotonin1A receptors exhibits an increase in membranes isolated from cholesterol-depleted neuronal cells. Our results gain pharmacological significance in view of the recently described structural evidence of specific cholesterol binding site(s) in GPCRs, and could be useful in designing better therapeutic strategies for neurodegenerative diseases associated with GPCRs