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.
Original language | English |
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Pages (from-to) | 17-29 |
Number of pages | 13 |
Journal | Experimental Neurobiology |
Volume | 28 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2019 |
Bibliographical note
Funding Information:This work was supported by the KIST Institutional Programs (Project No. 2E28412) and the NRF Brain Research Program (2016M3C7A1913845).
Publisher Copyright:
Copyright © Experimental Neurobiology 2019.
Keywords
- 5-HT receptor
- Neuro-oncological ventral antigen 1
- Neurological diseases
- RNA binding proteins
- Serotonin
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience