Physical and Functional Interaction between 5-HT₆ Receptor and Nova-1
Experimental Neurobiology
;
: 17-29, 2019.
Artigo
em Inglês
| 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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Transtornos Psicóticos
/
Encéfalo
/
Precursores de RNA
/
Serotonina
/
Linhagem Celular
/
Hormônio Liberador de Gonadotropina
/
Proteínas de Ligação a RNA
/
Transtornos do Humor
/
Técnicas do Sistema de Duplo-Híbrido
/
Citoplasma
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Experimental Neurobiology
Ano de publicação:
2019
Tipo de documento:
Artigo
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