Impact of RNA editing on functions of the serotonin 2C receptor in vivo

Frontiers in Neuroscience

Uade B Olaghere Da Silva¹  David CAirey¹  Clinton ECanal¹  Michael VMorabito¹  Elaine Sanders-Bush¹  Ronald BEmeson¹ 

[1] Vanderbilt University School of Medicine;

关键词: Behavior;    RNA Editing;    Serotonin;    Signal Transduction;    5-HT2C;    5-HT2C agonist;   

DOI  :  10.3389/neuro.23.001.2010

来源: DOAJ

【 摘 要 】

Transcripts encoding 5-HT2C receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms.In recombinant cells, the fully edited isoform, 5-HT2C-VGV, exhibits blunted G-protein coupling and reduced constitutive activity.The present studies examine the signal transduction properties of 5-HT2C-VGV receptors in brain to determine the in vivo consequences of altered editing.Using mice solely expressing the 5-HT2C-VGV receptor (VGV/Y), we demonstrate reduced G-protein coupling efficiency and high-affinity agonist binding of brain 5-HT2C-VGV receptors.However, enhanced behavioral sensitivity to a 5-HT2Creceptor agonist was also seen in mice expressing 5-HT2C-VGV receptors, an unexpected finding given the blunted G-protein coupling. In addition,mice expressing 5-HT2C-VGV receptors had greater sensitivity to a 5-HT2Cinverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT2C receptor binding sites in the brains of mice solely expressing -5HT2C-VGV receptors.We conclude that 5-HT2C-VGV receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5HT2C receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT2C receptor binding sites in brain. We further caution that the pattern of 5-HT2C receptorRNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor.

【 授权许可】

Unknown