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Serotonin 2C Receptors: Suicide, Serotonin, and Runaway RNA EditingDepartment of Psychiatry and Neuroscience Columbia University College of Physicians & Surgeons and New York State Psychiatric Institute, schmauss{at}neuron.cpmc.columbia.edu Transcripts of the gene encoding the serotonin 2C receptor are modified by RNA editing, a posttranscriptional process that converts adenosines to inosines. This editing changes up to three genomically encoded amino acids located in the second intracellular loop of the G-protein-coupled receptor. Compared with nonedited receptors, extensively edited receptor isoforms activate G protein less efficiently. Studies on mice revealed that 5-HT2C pre-mRNA editing is regulated in a serotonin-dependent manner, and postmortem studies on brain tissues of patients with schizophrenia and major depression found distinct site- specific alterations of this editing in the prefrontal cortex, a brain region expressing a large number of differently edited 5-HT2C mRNA isoforms. At present, the most complex alterations in 5-HT2C pre-mRNA editing were found in brains of depressed suicide victims. In these brains, 5-HT2C receptor isoforms with reduced function are expressed at significantly increased levels, suggesting that the regulation of editing by synaptic serotonin is defective.
Key Words: Serotonin • RNA editing • Serotonin 2C receptor • Prefrontal cortex • Major depression • Schizophrenia
The Neuroscientist, Vol. 9, No. 4,
237-242 (2003) This article has been cited by other articles:
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