Amitabha Chattopadhyay
Cholesterol-dependent Endocytosis and Trafficking of GPCRs: Implications in Pathophysiology and Therapeutics
Amitabha Chattopadhyay
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Centre for Cellular and Molecular Biology, Hyderabad, India
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G protein-coupled receptors (GPCRs) are the largest family of membrane proteins that relay extracellular signals across the plasma membrane and elicit an intricate cascade of cellular signaling events. A significantly large fraction of available drugs target GPCRs in order to exert fine control over functional outcomes from these receptors in pathological conditions. In this context, endocytosis and intracellular trafficking of GPCRs stringently regulate signaling outcomes from GPCRs within physiologically relevant spatiotemporal regimes. The membrane microenvironment around GPCRs has recently emerged as a key player in receptor function. Cholesterol is the single most abundant lipid in the eukaryotic plasma membrane and plays a central role in membrane organization and dynamics, with far-reaching functional implications in cellular physiology. In this talk, I will discuss current excitements in cholesterol-dependent endocytosis and trafficking of the serotonin1A receptor, a representative neurotransmitter GPCR, using confocal microscopy and FACS. We envision that a detailed understanding of the contribution of membrane lipids such as cholesterol in spatiotemporal regulation of GPCR signaling would enable the development of therapeutic interventions fine-tuned to receptors residing in specific membrane microenvironments.Â
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