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Exp Cell Res. 2010 May 1;316(8):1351-6. doi: 10.1016/j.yexcr.2010.02.034. Epub 2010 Mar 6.

Regulation of serotonin receptor function in the nervous system by lipid rafts and adaptor proteins.

Author information

1
Translational Neuropharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

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.

PMID:
20211176
DOI:
10.1016/j.yexcr.2010.02.034
[Indexed for MEDLINE]

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