title: Membrane cholesterol oxidation in live cells enhances the function of serotonin1Areceptors.
abstract: The serotonin1A(5-HT1A) receptor is an important neurotransmitter receptor that belongs to the G protein-coupled receptor (GPCR) family. It is implicated in a variety of cognitive and behavioral functions and serves as an important drug target for neuropsychiatric disorders such as anxiety and depression. Previous work from our laboratory has demonstrated that membrane cholesterol plays an important role in the function of the serotonin1Areceptor. Our earlier results highlighted several structural features of cholesterol essential for receptor function. In order to explore the importance of the hydroxyl group of cholesterol in the function of the serotonin1Areceptor, we utilized cholesterol oxidase to oxidize the hydroxyl group of cholesterol to keto group. Our results show that the oxidation of the hydroxyl group of cholesterol in live cells resulted in enhancement of agonist binding and G-protein coupling to the receptor with no appreciable change in overall membrane order. These results extend our understanding of the structural requirements of cholesterol for receptor function.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: jafri@ccmb.res.in.
authors.forename: Md
authors.initials: M
authors.lastname: Jafurulla
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Aswan
authors.initials: A
authors.lastname: Nalli
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: amit@ccmb.res.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D003412:Cricetulus; D006801:Humans; D010084:Oxidation-Reduction; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D002784:Cholesterol
keywords: Cholesterol; Cholesterol oxidase; Fluorescence anisotropy; G-protein coupling; Ligand binding