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Elucidation of the pathogenic mechanism in neuropsychiatric disorders by nuclear-cytoplasmic transport factors

Research Project

Project/Area Number 18K15044
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionUniversity of Fukui

Principal Investigator

Moriyama Tetsuji  福井大学, 学術研究院医学系部門, 助教 (50627990)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords核-細胞質間輸送因子 / エストロゲン受容体 / 核-細胞質間輸送 / 核-細胞質間輸送 / 精神疾患
Outline of Final Research Achievements

In most of the neuropsychiatric disorders, their pathogenic mechanisms are still unclear. Our aim is to clarify the regulation of brain function by importin-α1 and the pathogenesis of psychiatric-like behavioral abnormalities caused by its decreased expression. In this study, we mainly focused on the subcellular distribution and shuttling of estrogen receptor-α (ERα). Our research has demonstrated that Transportin-2 controls ERα nucleocytoplasmic shuttling by cytoplasmic retention and inhibition of importin-α/β1-dependent nuclear import, and thus plays a critical role in the proper regulation of the biological functions of ERα.

Academic Significance and Societal Importance of the Research Achievements

ERαは、主に核に存在する核内受容体であるが、核-細胞質間を常にシャトルしており、そのシャトルがエストロゲンシグナル伝達経路にとって非常に重要である。また、エストロゲンは、脳の海馬で高濃度に存在しており、スパインの密度と構造の変化を引き起こすことで認知機能を高める作用があることが報告されている。本研究により、ERαの核-細胞質間シャトリングメカニズムの解明や乳がん及び精神疾患の治療法の開発や創薬への応用が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-α2020

    • Author(s)
      Moriyama Tetsuji、Yoneda Yoshihiro、Oka Masahiro、Yamada Masami
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 18640-18640

    • DOI

      10.1038/s41598-020-75631-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 核輸送因子Kpna1ノックアウトマウスにおける行動異常の環境による増悪2020

    • Author(s)
      櫻井 航輝, 宮本 洋一, 盛山 哲嗣, 森田 真規子, 伊藤 大一, 岡 正啓, 疋田 貴俊
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Adolescent stress exacerbates behavioral deficits in Kpna1 knockout mice2020

    • Author(s)
      Sakurai K, Itou1 T, Morita M, Moriyama T, Miyamoto Y, Oka M, Hikida T.
    • Organizer
      The 12th Federation of European Neuroscience Societies Forum
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Estrogen receptor-αの核-細胞質間シャトリングにおけるTransportin-2 の重要な役割2020

    • Author(s)
      盛山 哲嗣, 米田 悦啓, 岡 正啓, 山田 雅己
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Analysis of molecular determinants of estrogen receptor α mobility2019

    • Author(s)
      Tetsuji Moriyama, Yoshihiro Yoneda, Masahiro Oka, Masami Yamada.
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of molecular determinants of estrogen receptor α mobility2018

    • Author(s)
      盛山 哲嗣、米田 悦啓、岡 正啓、山田 雅己
    • Organizer
      第70回日本細胞生物学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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