Exp Neurobiol 2019; 28(1): 17-29
Published online January 21, 2019
© The Korean Society for Brain and Neural Sciences
Soon-Hee Kim1,†, Misun Seo1, Hongik Hwang1, Dong-Min Moon1, Gi Hoon Son2, Kyungjin Kim3, and Hyewhon Rhim1,4*
1Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
2Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
3Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.
4Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea.
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-958-5923, FAX: 82-2-958-6937
†Present address: Division of Food Functionality, Korea Food Research Institute (KFRI), 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju 55365, Korea
5-HT6 receptor (5-HT6R) is implicated in cognitive dysfunction, mood disorder, psychosis, and eating disorders. However, despite its significant role in regulating the brain functions, regulation of 5-HT6R at the molecular level is poorly understood. Here, using yeast two-hybrid assay, we found that human 5-HT6R directly binds to neuro-oncological ventral antigen 1 (Nova-1), a brain-enriched splicing regulator. The interaction between 5-HT6R and Nova-1 was confirmed using GST pull-down and co-immunoprecipitation assays in cell lines and rat brain. The splicing activity of Nova-1 was decreased upon overexpression of 5-HT6R, which was examined by detecting the spliced intermediates of gonadotropin-releasing hormone (GnRH), a known pre-mRNA target of Nova-1, using RT-PCR. In addition, overexpression of 5-HT6R induced the translocation of Nova-1 from the nucleus to cytoplasm, resulting in the reduced splicing activity of Nova-1. In contrast, overexpression of Nova-1 reduced the activity and the total protein levels of 5-HT6R. Taken together, these results indicate that when the expression levels of 5-HT6R or Nova-1 protein are not properly regulated, it may also deteriorate the function of the other.