期刊
EXPERIMENTAL CELL RESEARCH
卷 316, 期 8, 页码 1351-1356出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2010.02.034
关键词
Caveolin; GPCR; Scaffolding proteins; Ligand bias
资金
- Vetenskapsradet
- Royal Academy of Sciences
- Soderberg Foundation
- Swedish Brain Fund
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. (C) 2010 Elsevier Inc. All rights reserved.
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