RNA Editing of the Human Serotonin 5-Hydroxytryptamine 2C Receptor Silences Constitutive Activity*
Journal of Biological Chemistry April 2, 1999 C. Niswender, Sara C. Copeland, K. Herrick‐Davis et al.
RNA transcripts encoding the serotonin 5-HT2C receptor undergo editing at up to five specific sites, altering the amino acid sequence. Human brain samples expressed higher levels of edited variants (5-HT2C-VSV and 5-HT2C-VGV) compared with rat brain. Agonist stimulation of nonedited and edited receptors expressed in fibroblasts showed that serotonergic agonists were less potent at the edited receptors. Competition binding experiments revealed a guanine nucleotide-sensitive serotonin high affinity state only for the nonedited receptor, indicating that editing reduces G protein coupling efficiency, primarily by silencing the constitutive activity of the nonedited receptor. These distinctions suggest RNA editing controls physiological signaling at serotonergic synapses.