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Physical and functional interaction between 5-HT receptor and nova

Experimental Neurobiology, ISSN: 2093-8144, Vol: 28, Issue: 1, Page: 17-29
2019
  • 6
    Citations
  • 0
    Usage
  • 19
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    6
    • Citation Indexes
      6
  • Captures
    19

Article Description

5-HT receptor (5-HTR) is implicated in cognitive dysfunction, mood disorder, psychosis, and eating disorders. However, despite its significant role in regulating the brain functions, regulation of 5-HTR at the molecular level is poorly understood. Here, using yeast two-hybrid assay, we found that human 5-HTR directly binds to neuro-oncological ventral antigen 1 (Nova-1), a brain-enriched splicing regulator. The interaction between 5-HTR 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-HTR, 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-HTR 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-HTR. Taken together, these results indicate that when the expression levels of 5-HTR or Nova-1 protein are not properly regulated, it may also deteriorate the function of the other.

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