Possible interaction of serotonin 2C receptor mRNA editing at C-site with expression of microtubule-associated protein 2 and neurite outgrowth in rat cultured cortical cells

The serotonin 2C receptor (5-HT2CR) is widely distributed in the central nervous system and participates in a variety of brain functions and mental diseases such as depression.1 The 5-HT2CR mRNA, as well as genes encoding receptors such as the AMPA type glutamate receptor,2 the potassium channel KCNA13 and GABAA receptor subunit α34 undergoes adenosine-to-inosine RNA editing5 mediated by adenosine deaminases acting on RNA (ADARs).6,7 Although RNA editing in non-coding regions is common to all types of animals,8 theses receptors have been reported to undergo editing in their coding regions. However, the functional significance of 5-HT2CR mRNA editing remains to be clarified. There are five editing sites, named A, B, E (C’), C and D from the 5’side, in 5-HT2CR mRNA.9,10 All of the sites are located near each other in the region encoding the second intracellular loop of 5-HT2CR mRNA.9,10 The isoforms of 5-HT2CR synthesized from the edited mRNA have a decreased ability to activate G protein, as compared to the unedited isoform. We previously reported the C-site editing give an unique character to membrane signal transduction through G protein by using the Xenopus oocyte system injected with mutated cRNAs in 5-HT2CR editing sites.11