Establishment and characterization of RNA-edited serotonin 2C receptor isoform cell models and alteration of amyloid precursor protein ectodomain secretion in HEK293 APPSwe cells

RNA editing is a mechanism for generating molecular diversity by altering the genetic code at the level of RNA. The 5-HT2C receptor is the only G protein-coupled receptor known to be edited. It has been reported that the non-edited 5-HT2C receptor stimulates secretion of the APP metabolite APP ectodomain (APPs). However, it remains unknown whether RNA-edited 5-HT2C receptors can also affect APPs secretion. In this study, cDNAs of five non-edited or partially/fully edited 5-HT2C receptor isoforms (INI, VNI, VNV, VSV and VGV) were stably transfected into HEK293APPSwe cells to detect the cell proliferation and APPs secretion. The results demonstrated that the overexpression of INI and VNI caused increased proliferation of host cells while VNV, VSV and VGV caused inverse effects (P < 0.01). Compared with both control and non-edited isoform INI, APPs levels were significantly increased in the four edited 5-HT2C receptor isoforms, VNI (P < 0.05), VNV (P < 0.05), VSV (P < 0.05) and VGV (P < 0.01). These results suggest that the RNA editing of the 5-HT2C receptor may affect APPs secretion through different signaling pathways related to cell growth and protein processing, and that these cell models will provide appropriate useful information to study the association between the RNA editing of the serotonin 5-HT2C receptor and APP metabolism.