TY - JOUR
T1 - Physical and functional interaction between 5-HT6 receptor and nova
AU - Kim, Soon Hee
AU - Seo, Misun
AU - Hwang, Hongik
AU - Moon, Dong Min
AU - Son, Gi Hoon
AU - Kim, Kyungjin
AU - Rhim, Hyewhon
N1 - 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.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - 5-HT receptor
KW - Neuro-oncological ventral antigen 1
KW - Neurological diseases
KW - RNA binding proteins
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=85067888899&partnerID=8YFLogxK
U2 - 10.5607/en.2019.28.1.17
DO - 10.5607/en.2019.28.1.17
M3 - Article
AN - SCOPUS:85067888899
SN - 1226-2560
VL - 28
SP - 17
EP - 29
JO - Experimental Neurobiology
JF - Experimental Neurobiology
IS - 1
ER -