title: RNA editing of the human serotonin 5-HT2C receptor alters receptor-mediated activation of G13 protein.
abstract: The recent completion of the human genome predicted the presence of only 30,000 genes, stressing the importance of mechanisms that increase molecular diversity at the post-transcriptional level. One such post-transcriptional event is RNA editing, which generates multiple protein isoforms from a single gene, often with profound functional consequences. The human serotonin 5-HT(2C) receptor undergoes RNA editing that creates multiple receptor isoforms. One consequence of RNA editing of cell surface receptors may be to alter the pattern of activation of heterotrimeric G-proteins and thereby shift preferred intracellular signaling pathways. We examined the ability of the nonedited 5-HT(2C) receptor isoform (INI) and two extensively edited isoforms, VSV and VGV, to interact with various G-protein alpha subunits. Two functional assays were utilized: the cell-based functional assay, Receptor Selection/Amplification Technology(TM), in which the pharmacological consequences of co-expression of 5HT(2C) receptor isoforms with G-protein alpha subunits in fibroblasts were studied, and 5HT(2C) receptor-mediated rearrangements of the actin cytoskeleton in stable cell lines. These studies revealed that the nonedited 5-HT(2C) receptor functionally couples to G(q) and G(13). In contrast, coupling to G(13) was not detected for the extensively edited 5-HT(2C) receptors. Thus, RNA editing represents a novel mechanism for regulating the pattern of activation of heterotrimeric G-proteins, molecular switches that control an enormous variety of biological processes.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-6600, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Price
authors.forename: D M
authors.initials: DM
authors.lastname: Weiner
authors.forename: M S
authors.initials: MS
authors.lastname: Chang
authors.forename: E
authors.initials: E
authors.lastname: Sanders-Bush
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010716:Phosphatidylinositols / Q000378:metabolism; D020033:Protein Isoforms; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D010455:Peptides; D010716:Phosphatidylinositols; D020033:Protein Isoforms; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D019204:GTP-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13