| First Author | Olaghere da Silva UB | Year | 2010 |
| Journal | Front Neurosci | Volume | 4 |
| Pages | 26 | PubMed ID | 20582266 |
| Mgi Jnum | J:288778 | Mgi Id | MGI:6433417 |
| Doi | 10.3389/neuro.23.001.2010 | Citation | Olaghere da Silva UB, et al. (2010) Impact of RNA editing on functions of the serotonin 2C receptor in vivo. Front Neurosci 4:26 |
| abstractText | Transcripts encoding 5-HT(2C) receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT(2C-VGV), exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT(2C-VGV) receptors in brain to determine the in vivo consequences of altered editing. Using mice solely expressing the 5-HT(2C-VGV) receptor (VGV/Y), we demonstrate reduced G-protein coupling efficiency and high-affinity agonist binding of brain 5-HT(2C-VGV) receptors. However, enhanced behavioral sensitivity to a 5-HT(2C) receptor agonist was also seen in mice expressing 5-HT(2C-VGV) receptors, an unexpected finding given the blunted G-protein coupling. In addition, mice expressing 5-HT(2C-VGV) receptors had greater sensitivity to a 5-HT(2C) inverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT(2C) receptor binding sites in the brains of mice solely expressing 5-HT(2C-VGV) receptors. We conclude that 5-HT(2C-VGV) receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5-HT(2C) receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT(2C) receptor binding sites in brain. We further caution that the pattern of 5-HT(2C) receptor RNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor. |
