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Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
Published on: March 25, 2020
Membrane cholesterol oxidation in live cells enhances the function of serotonin1A receptors
Md Jafurulla1, Aswan Nalli1, Amitabha Chattopadhyay1
1CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
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 serotonin1A receptor. 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 serotonin1A receptor, 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.
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