Prasad Rajesh, Paila Yamuna Devi, Chattopadhyay Amitabha
Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
Biochem Biophys Res Commun. 2009 Dec 4;390(1):93-6. doi: 10.1016/j.bbrc.2009.09.072. Epub 2009 Sep 23.
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 serotonin(1A) 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 serotonin(1A) 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.
神经系统中细胞的膜脂质组成独特且具有显著的多样性。中枢神经系统中的胆固醇代谢与稳态及其在神经元功能中的作用是神经病理发生的重要决定因素。5-羟色胺（1A）受体是G蛋白偶联受体超家族的重要成员，参与多种认知、行为和发育功能。我们在此首次报告，从胆固醇耗竭的神经元细胞中分离出的膜中，人5-羟色胺（1A）受体的配体结合功能有所增强。鉴于最近描述的G蛋白偶联受体中特定胆固醇结合位点的结构证据，我们的结果具有药理学意义，并且可能有助于设计针对与G蛋白偶联受体相关的神经退行性疾病的更好治疗策略。
