TY - JOUR T1 - RNA Editing of the Human Serotonin 5-HT<sub>2C</sub> Receptor Disrupts Transactivation of the Small G-Protein RhoA JF - Molecular Pharmacology JO - Mol Pharmacol SP - 252 LP - 256 DO - 10.1124/mol.65.1.252 VL - 65 IS - 1 AU - Lori McGrew AU - Raymond D. Price AU - Elizabeth Hackler AU - Mike S. S. Chang AU - Elaine Sanders-Bush Y1 - 2004/01/01 UR - http://molpharm.aspetjournals.org/content/65/1/252.abstract N2 - The human serotonin 5-HT2C receptor undergoes adenosineto-inosine RNA editing at five positions, generating multiple receptor isoforms with altered G-protein coupling properties. In the current study, we demonstrate that RNA editing regulates the pattern of intracellular signaling. The non-edited human 5-HT2C receptor isoform INI activates phospholipase D via the G13 heterotrimer G-protein. We present evidence that transactivation of the small G-protein RhoA is required for phospholipase D activation. In contrast, neither transactivation of RhoA nor phospholipase D activation was detected in cells expressing the fully edited VGV isoform. The ability to activate phospholipase C is also reduced in VGV-expressing cells, but not to the extent found for the phospholipase D signal. We conclude that RNA editing represents a novel mechanism for regulating 5-HT2C receptor signaling to pathways linked to actin cytoskeletal organization and regulated exocytosis. ER -