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Exploration of substrate proteins of calmodulin kinase II by using the kinase-dead knock-in mouse.

Research Project

Project/Area Number 16K08511
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

YAMAGATA Yoko  生理学研究所, 助教 (20210338)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords蛋白質リン酸化 / キナーゼ / 学習・記憶 / 行動テスト / 記憶・学習 / シグナル伝達 / 神経科学 / 生体分子 / 生理学 / 脳・神経
Outline of Final Research Achievements

To understand higher-order brain functions, especially learning and memory, and to contribute to the prevention and treatment of human diseases, molecular analyses of their mechanisms are essential. In this study, I made exploration of substrate proteins of calmodulin kinase IIα, one of the representative protein kinases in the brain that are indispensable for learning and memory, by using functionally modified, genetically engineered mice. At the same time, I showed that there is brain regional specificity in the molecular mechanisms of learning and memory, and made selection of appropriate behavioral memory tests for the evaluation of substrate proteins. These studies will be useful for further understanding of human brain functions and contribute to the prevention and treatment of human brain disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、蛋白質リン酸化酵素の基質蛋白質の探索にとって機能的遺伝子改変マウスの活用が有用であること、また、脳の機能的部位に特化した解析が重要であることが判明した。今後さらに探索した基質候補蛋白質の同定を進め、実際の生体における学習・記憶の時間的経過と共に、どのようにリン酸化状態が変化するのか、また病態とどのように関連するのかを明らかにすることにより、学習・記憶に障害を来すヒト疾患の予防・治療に貢献することが期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 1 results) Remarks (10 results)

  • [Journal Article] Differential Involvement of Kinase Activity of Ca2+/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse.2018

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K.
    • Journal Title

      eNeuro

      Volume: 5 Issue: 4 Pages: 0133-18

    • DOI

      10.1523/eneuro.0133-18.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase IIα and Rap12017

    • Author(s)
      Cornelia Koeberle Solveigh、Tanaka Shinji、Kuriu Toshihiko、Iwasaki Hirohide、Koeberle Andreas、Schulz Alexander、Helbing Dario-Lucas、Yamagata Yoko、Morrison Helen、Okabe Shigeo
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 13409-13409

    • DOI

      10.1038/s41598-017-13728-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Kinase-dead knock-in mouse revealed differential involvement of kinase activity of Ca2+/calmodulin-dependent protein kinase II alpha in hippocampus- and amygdala-dependent memory2019

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      第8回生理研・霊長研・新潟脳研合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Differential contribution of calmodulin kinase II alpha in hippocampus- and amygdala-dependent memory2018

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      The 49th NIPS International Symposium "Ion channels: looking back, seeing ahead"
    • Related Report
      2018 Annual Research Report
  • [Presentation] Involvement of calmodulin kinase IIalpha in hippocampus- vs. amygdala-dependent memory revealed by kinase-dead knock-in mouse2018

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海馬記憶と扁桃体記憶は、カルモジュリンキナーゼIIα活性によって異なる制御を受けている2018

    • Author(s)
      山肩葉子, 柳川右千夫, 井本敬二
    • Organizer
      第8回名古屋大学医学研究科・生理学研究所合同シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Differential involvement of calmodulin kinase IIα in hippocampus- and amygdala-dependent memory - Analysis using the kinase-dead knock-in mouse2018

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] カルモジュリンキナーゼIIα活性と加齢・海馬依存性記憶2017

    • Author(s)
      山肩葉子, 柳川右千夫, 井本敬二
    • Organizer
      第7回名古屋大学医学研究科・生理学研究所合同シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Calmodulin kinase IIα, aging and spatial memory - Analysis using the kinase-dead knock-in mouse2017

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] How much kinase activity of Calmodulin kinase IIα is necessary to acquire hippocampus-dependent memory?2016

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      The 47th NIPS International Symposium "Decoding Synapses"
    • Place of Presentation
      岡崎コンファレンスセンター, 愛知県, 岡崎市
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report
  • [Presentation] カルモジュリンキナーゼIIα活性による海馬依存性記憶の特異的制御.2016

    • Author(s)
      山肩葉子, 柳川右千夫, 井本敬二
    • Organizer
      第6回名古屋大学医学研究科・生理学研究所合同シンポジウム
    • Place of Presentation
      名古屋大学, 愛知県, 名古屋市
    • Related Report
      2016 Research-status Report
  • [Presentation] Kinase activity of Ca2+/calmodulin-dependent protein kinase IIα and hippocampus- and amygdala-dependent memory - Dose-response relationship revealed by the kinase-dead knock-in mouse.2016

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会合同年会
    • Place of Presentation
      福岡国際会議場, 福岡県, 福岡市
    • Related Report
      2016 Research-status Report
  • [Presentation] Differential involvement of kinase activity of Ca2+/calmodulin-dependent protein kinase IIα in hippocampus- and amygdala-dependent memory - Behavioral analysis of heterozygous kinase-dead knock-in mouse.2016

    • Author(s)
      Yamagata Y, Yanagawa Y, Imoto K
    • Organizer
      第39回日本神経科学大会, Neuroscience 2016
    • Place of Presentation
      パシフィコ横浜, 神奈川県, 横浜市
    • Related Report
      2016 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所 研究報告(日本語版)

    • URL

      http://www.nips.ac.jp/nips_research/2018/09/ii.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 自然科学研究機構生理学研究所 研究報告(英語版)

    • URL

      http://www.nips.ac.jp/nips_research/eng/2018/09/ii.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 自然科学研究機構生理学研究所 研究部門紹介(日本語版)

    • URL

      https://www.nips.ac.jp/research/group/post-53/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 自然科学研究機構生理学研究所 研究部門紹介(英語版)

    • URL

      https://www.nips.ac.jp/eng/research/group/post-53/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ 研究内容

    • URL

      http://www.nips.ac.jp/huinfo/research/ns_Res05.htm

    • Related Report
      2017 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ 研究内容(英語版)

    • URL

      http://www.nips.ac.jp/huinfo/research/ns_Res05_E.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ 論文リスト

    • URL

      http://www.nips.ac.jp/huinfo/publications/index.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ

    • URL

      http://www.nips.ac.jp/huinfo/research/ns_Res05.htm

    • Related Report
      2016 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ

    • URL

      http://www.nips.ac.jp/huinfo/research/ns_Res05_E.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 自然科学研究機構生理学研究所神経シグナル研究部門ホームページ

    • URL

      http://www.nips.ac.jp/huinfo/publications/index.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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