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J. Biol. Chem., Vol. 276, Issue 48, 44663-44668, November 30, 2001
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From the 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-HT2C 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-HT2C receptor isoform (INI) and two extensively edited
isoforms, VSV and VGV, to interact with various G-protein
RNA Editing of the Human Serotonin 5-HT2C
Receptor Alters Receptor-mediated Activation of G13
Protein*
,, and¶
Department of Pharmacology, Vanderbilt
University, Nashville, Tennessee 37232-6600 and § ACADIA
Pharmaceuticals and the Departments of Neurosciences and Psychiatry,
University of California, San Diego, La Jolla, California 92121
subunits. Two functional assays were utilized: the cell-based
functional assay, Receptor Selection/Amplification TechnologyTM, in which the pharmacological consequences of
co-expression of 5HT2C receptor isoforms with G-protein subunits in fibroblasts were studied, and 5HT2C
receptor-mediated rearrangements of the actin cytoskeleton in stable
cell lines. These studies revealed that the nonedited
5-HT2C receptor functionally couples to Gq and
G13. In contrast, coupling to G13 was not
detected for the extensively edited 5-HT2C 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.
*
This work was supported by National Institutes of Health
Grants MH34007, NS35891, and GM07623.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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