Regulation of serotonin receptor function in the nervous system by lipid rafts and adaptor proteins |
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Authors: | Karl Bjö rk |
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Affiliation: | Translational Neuropharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden |
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Abstract: | 5-HT is a phylogenetically conserved monoaminergic neurotransmitter which is crucial for a number of physiological processes and is dysregulated in several disease states including depression, anxiety and schizophrenia. 5-HT neurons in the central nervous system are localized in the raphe nuclei and project to a wide range of target areas. 5-HT exerts its functions through 14 subtypes of 5-HT receptors. The tertiary structures of seven transmembrane 5-HT receptors contain several important features, including cholesterol consensus motifs, prominent intracellular loops and free C-termini. Alterations of cholesterol levels affect binding of ligands to 5-HT receptors and cholesterol-enriched microdomains in the cell membrane, termed lipid rafts, regulate 5-HT receptor internalization and signaling. The intracellular loops and the C-termini of 5-HT receptors provide binding sites for interacting adaptor proteins. Adaptor proteins affect internalization, desensitization as well as G-protein dependent and independent signaling via 5-HT receptors. We will here briefly review recent progress on the role of lipid rafts and adaptor proteins in the regulation of localization, trafficking, signaling and ligand bias of 5-HT receptors. |
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Keywords: | Serotonin, 5-HT CNS, Central Nervous System GPCR, G-protein coupled receptor CCM, Cholesterol Consensus Motif MβCD, Methyl-β-cyclodextrin Cav-1, Caveolin 1 protein CREB, Cyclic AMP responsive element binding protein ERK, Extracellular regulated kinase PSD-95, Post-synaptic density 95 protein PDZ, PSD-95-disc-large-zonula occludens GRK, GPCR-regulated kinase DOI, 2, 5-dimethoxy-4-iodamphetamine |
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