title: Molecular rheology of neuronal membranes explored using a molecular rotor: Implications for receptor function.
abstract: The role of membrane cholesterol as a crucial regulator in the structure and function of membrane proteins and receptors is well documented. However, there is a lack of consensus on the mechanism for such regulation. We have previously shown that the function of an important neuronal receptor, the serotonin1A receptor, is modulated by cholesterol in hippocampal membranes. With an overall objective of addressing the role of membrane physical properties in receptor function, we measured the viscosity of hippocampal membranes of varying cholesterol content using a meso-substituted fluorophore (BODIPY-C12) based on the BODIPY probe. BODIPY-C12 acts as a fluorescent molecular rotor and allows measurement of hippocampal membrane viscosity through its characteristic viscosity-sensitive fluorescence depolarization. A striking feature of our results is that specific agonist binding by the serotonin1A receptor exhibits close correlation with hippocampal membrane viscosity, implying the importance of global membrane properties in receptor function. We envision that our results are important in understanding GPCR regulation by the membrane environment, and is relevant in the context of diseases in which GPCR signaling plays a major role and are characterized by altered membrane fluidity.
authors.affiliation: CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Sreetama
authors.initials: S
authors.lastname: Pal
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India; School of Chemistry, Sambalpur University, Burla, Odisha 768 019, India.
authors.forename: Hirak
authors.initials: H
authors.lastname: Chakraborty
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Bandari
authors.affiliation: Antikor Biopharma Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage SG1 2FX, Herts, UK.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Yahioglu
authors.affiliation: Department of Physics, King's College London, Strand, London WC2R 2LS, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Suhling
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, New Delhi, India. Electronic address: amit@ccmb.res.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012212:Rheology; D013050:Spectrometry, Fluorescence
keywords: Cholesterol; Hippocampal membrane; Molecular rotor; Neuronal receptor; Viscosity