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Study on the control of stress response in the brain via the regulation of protein translation and gene transcription by eEF1BdeltaL

Research Project

Project/Area Number 18K06876
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionInternational University of Health and Welfare (2020)
Kumamoto University (2018-2019)

Principal Investigator

Kaitsuka Taku  国際医療福祉大学, 福岡薬学部, 講師 (00435926)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords翻訳伸長因子 / 選択的スプライシング / 転写因子 / 分子シャペロン / ストレス応答 / てんかん / タンパク質合成 / 脱リン酸化 / 下垂体前葉ホルモン / タンパク質翻訳 / タンパク質翻訳因子 / 神経発達障害 / 遺伝子転写
Outline of Final Research Achievements

In this study, we investigated the cellular function of eEF1BdeltaL which is a brain-specific splicing variant of translation elongation factor eEF1Bdelta1. In addition, we attempted to clarify the mechanism about how epileptic seizure which occurs in eEF1BdeltaL knockout mice. As a result, it is found that eEF1BdeltaL interacts with binding partners of eEF1Bdelta1 and protein phosphatase 1. In addition, knockout of eEF1BdeltaL leads to augmented protein synthesis and increased phosphorylation of ERK1/2. It is generally accepted that such increased phosphorylation of ERK1/2 is the cause of audiogenic seizures in a mouse model of an intellectual disability. From the above, the present results suggest the molecular mechanism of eEF1BdeltaL and how its knockout leads to epileptic behavior.

Academic Significance and Societal Importance of the Research Achievements

選択的スプライシング機構は有限の遺伝子から多様なタンパク質を生み出す精巧な細胞機能であり、進化における脳の複雑化に寄与してきたと言われている。本研究の対象であるeEF1BδLは高等動物にのみ発現するスプライシングバリアントであり、その機能を解明することは複雑なヒト脳の成り立ちを理解する鍵となり、学術的に意義深い。
eEF1BδLをコードする遺伝子EEF1Dについて、その機能喪失型変異が知的障害と関連することが報告されている。知的障害ではてんかんを併発することが多く、本研究の成果であるeEF1BδLの機能とその欠損によるてんかん発症に関する情報は上記の遺伝子疾患を理解する上で重要である。

Report

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

    (20 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (6 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Wright State University(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] NYU Langone Medical Center(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] NYU Langone Medical Center(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Phagocytic activity of splenic macrophages is enhanced and accompanied by cytosolic alkalinization in TRPM7 kinase‐dead mice2021

    • Author(s)
      Beesetty Pavani、Rockwood Jananie、Kaitsuka Taku、Zhelay Tetyana、Hourani Siham、Matsushita Masayuki、Kozak J. Ashot
    • Journal Title

      The FEBS Journal

      Volume: - Issue: 11 Pages: 3585-3601

    • DOI

      10.1111/febs.15683

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Response of Pluripotent Stem Cells to Environmental Stress and Its Application for Directed Differentiation2021

    • Author(s)
      Kaitsuka Taku、Hakim Farzana
    • Journal Title

      Biology

      Volume: 10 Issue: 2 Pages: 84-84

    • DOI

      10.3390/biology10020084

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat Shock-Induced Dephosphorylation of Eukaryotic Elongation Factor 1BδL by Protein Phosphatase 12021

    • Author(s)
      Kaitsuka Taku、Tomizawa Kazuhito、Matsushita Masayuki
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 7 Pages: 598578-598578

    • DOI

      10.3389/fmolb.2020.598578

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIRT2 inhibition activates hypoxia-inducible factor 1α signaling and mediates neuronal survival2020

    • Author(s)
      Kaitsuka Taku、Matsushita Masayuki、Matsushita Nobuko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 4 Pages: 957-962

    • DOI

      10.1016/j.bbrc.2020.06.159

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM7 channel activity in Jurkat T lymphocytes during magnesium depletion and loading: implications for divalent metal entry and cytotoxicity2020

    • Author(s)
      Mellott Alayna、Rockwood Jananie、Zhelay Tetyana、Luu Charles Tuan、Kaitsuka Taku、Kozak J. Ashot
    • Journal Title

      Pflugers Archiv - European Journal of Physiology

      Volume: 472 Issue: 11 Pages: 1589-1606

    • DOI

      10.1007/s00424-020-02457-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 翻訳伸長因子Eef1dの変異が引き起こすてんかん様発作とその発症メカニズムに関する研究2020

    • Author(s)
      貝塚 拓
    • Journal Title

      BIO Clinica

      Volume: 35 Pages: 92-95

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Response to Stimulations Inducing Circadian Rhythm in Human Induced Pluripotent Stem Cells2020

    • Author(s)
      Kaneko Hitomi、Kaitsuka Taku、Tomizawa Kazuhito
    • Journal Title

      Cells

      Volume: 9 Issue: 3 Pages: 620-620

    • DOI

      10.3390/cells9030620

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] eEF1BδL欠損で生じる聴原性発作2020

    • Author(s)
      貝塚 拓
    • Journal Title

      Medical Science Digest

      Volume: 46 Pages: 111-114

    • Related Report
      2019 Research-status Report
  • [Journal Article] A culture substratum with net-like polyamide fibers promotes the differentiation of mouse and human pluripotent stem cells to insulin-producing cells2019

    • Author(s)
      Kaitsuka Taku、Kojima Rie、Kawabe Masaaki、Noguchi Hirofumi、Shiraki Nobuaki、Kume Shoen、Tomizawa Kazuhito
    • Journal Title

      Biomedical Materials

      Volume: 14 Issue: 4 Pages: 045019-045019

    • DOI

      10.1088/1748-605x/ab261c

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deletion of Long Isoform of Eukaryotic Elongation Factor 1Bδ Leads to Audiogenic Seizures and Aversive Stimulus-Induced Long-Lasting Activity Suppression in Mice.2018

    • Author(s)
      Kaitsuka, T., Kiyonari, H., Shiraishi, A., Tomizawa, K., Matsushita, M
    • Journal Title

      Front. Mol. Neurosci.

      Volume: 11 Pages: 358-358

    • DOI

      10.3389/fnmol.2018.00358

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 熱ストレス応答タンパク質eEF1BδLのリン酸化/脱リン酸化による機能 制御2021

    • Author(s)
      貝塚 拓、高松 岳矢、片桐 千秋、松下 正之
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒトiPS細胞の概日リズム特性に関する研究2020

    • Author(s)
      金子 瞳、貝塚 拓、富澤 一仁
    • Organizer
      第27回日本時間生物学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 網目構造の合成繊維シートから成る培養担体は多能性幹細胞の膵臓系譜への分化を促進する2019

    • Author(s)
      貝塚 拓, 小島 理恵, 川部 雅章, 野口 洋文, 白木 伸明, 粂 昭苑, 富澤 一仁
    • Organizer
      日本組織培養学会 第92回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒトiPS細胞の概日リズムの同調刺激に対する反応とそのメカニズムに関する研究2019

    • Author(s)
      金子 瞳, 貝塚 拓, 富澤 一仁
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 翻訳因子の長鎖アイソフォームeEF1BδLの欠損マウスは聴原生てんかんを呈する2018

    • Author(s)
      貝塚 拓、富澤 一仁、松下 正之
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of brain-specific splicing of Eef1d and activity control of its nuclear variant, eEF1BδL by stress-induced dephosphorylation2018

    • Author(s)
      Taku Kaitsuka, Masayuki Matsushita
    • Organizer
      NEUROSCIENCE 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] researchmap

    • URL

      http://researchmap.jp/read0108060

    • Related Report
      2020 Annual Research Report 2019 Research-status Report 2018 Research-status Report

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

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