Physical and Functional Interaction between 5-HT₆ Receptor and Nova-1
- Author:
Soon Hee KIM
1
;
Misun SEO
;
Hongik HWANG
;
Dong Min MOON
;
Gi Hoon SON
;
Kyungjin KIM
;
Hyewhon RHIM
Author Information
- Publication Type:Original Article
- Keywords: Serotonin; 5-HT₆ receptor; Neuro-oncological ventral antigen 1; RNA binding proteins; Neurological diseases
- MeSH: Animals; Brain; Cell Line; Cytoplasm; Eating; Gonadotropin-Releasing Hormone; Humans; Immunoprecipitation; Mood Disorders; Psychotic Disorders; Rats; RNA Precursors; RNA-Binding Proteins; Serotonin; Two-Hybrid System Techniques
- From:Experimental Neurobiology 2019;28(1):17-29
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
