Kim, Soon-Hee Seo, Misun Hwang, Hongik Moon, Dong-Min Son, Gi Hoon Kim, Kyungjin Rhim, Hyewhon 2024-01-19T21:01:00Z 2024-01-19T21:01:00Z 2021-09-02 2019-02 1226-2560 https://pubs.kist.re.kr/handle/201004/120402 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. English KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE Physical and Functional Interaction between 5-HT6 Receptor and Nova-1 Article 10.5607/en.2019.28.1.17 1 Experimental Neurobiology, v.28, no.1, pp.17 - 29 Experimental Neurobiology 28 1 17 29 N scie scopus kci ART002444277 000460388900002 2-s2.0-85067888899 Medicine, Research & Experimental Neurosciences Research & Experimental Medicine Neurosciences & Neurology Article INHIBITION SB-399885 ANTIGEN RNA-BINDING PROTEINS ANTAGONIST DISEASE MODELS ANTIDEPRESSANT LOCALIZATION RECOGNITION Serotonin 5-HT6 receptor Neuro-oncological ventral antigen 1 RNA binding proteins Neurological diseases