Physical and Functional Interaction between 5-HT₆ Receptor and Nova-1
Experimental Neurobiology
;
: 17-29, 2019.
Article
in English
| WPRIM
| ID: wpr-739534
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Psychotic Disorders
/
Brain
/
RNA Precursors
/
Serotonin
/
Cell Line
/
Gonadotropin-Releasing Hormone
/
RNA-Binding Proteins
/
Mood Disorders
/
Two-Hybrid System Techniques
/
Cytoplasm
Limits:
Animals
/
Humans
Language:
English
Journal:
Experimental Neurobiology
Year:
2019
Type:
Article
Similar
MEDLINE
...
LILACS
LIS