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Study on regulatory mechanism of neural activity and emotional behavior by intracellular signals

Research Project

Project/Area Number 17H01380
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology / General neuroscience
Research InstitutionNagoya University

Principal Investigator

Kaibuchi Kozo  名古屋大学, 医学系研究科, 教授 (00169377)

Co-Investigator(Kenkyū-buntansha) 永井 拓  藤田医科大学, その他部局等, 教授 (10377426)
天野 睦紀  名古屋大学, 医学系研究科, 准教授 (90304170)
西岡 朋生  名古屋大学, 医学系研究科, 助教 (70435105)
黒田 啓介  名古屋大学, 医学系研究科, 特任助教 (80631431)
船橋 靖広  藤田医科大学, 総合医科学研究所, 講師 (00749913)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2019: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2017: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywords細胞内シグナル / リン酸化プロテオミクス解析 / ニューロモジュレーター / 情動行動 / 学習・記憶 / 神経活動 / シナプス可塑性 / 遺伝子発現 / 神経科学 / シグナル伝達 / リン酸化 / プロテオミクス解析 / 学習
Outline of Final Research Achievements

In this study, we comprehensively identified proteins that are phosphorylated downstream of neuromodulators (dopamine, adenosine, acetylcholine) and glutamate using our proprietary phospho-proteomics method. We have elucidated the intracellular signal transduction that regulates neuronal excitatory, synaptic plasticity, and gene expression at the molecular level, and also elucidated the regulatory mechanism of emotional behavior and its learning & memory.

Academic Significance and Societal Importance of the Research Achievements

グルタミン酸やニューロモジュレーター(ドーパミン、アデノシン、アセチルコリン)の下流で働くキナーゼの主要な基質が明らかになり、神経細胞の興奮性やシナプス可塑性、遺伝子発現の制御機構が明らかになった。さらに、これらの神経活動と情動行動・学習との関連が明らかになった。これらの成果は基礎神経科学において重要というだけでなく、様々な精神・神経疾患の病態解明や診断・治療法の確立等の医学分野に貢献する可能性が高いと考えられる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (36 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (21 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Remarks (4 results)

  • [Journal Article] Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK2021

    • Author(s)
      Ariza Anthony、Funahashi Yasuhiro、Kozawa Sachi、Omar Faruk Md.、Nagai Taku、Amano Mutsuki、Kaibuchi Kozo
    • Journal Title

      Journal of Neurochemistry

      Volume: - Issue: 6 Pages: 1774-1788

    • DOI

      10.1111/jnc.15303

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prickle2 and Igsf9b Coordinately Regulate the Cytoarchitecture of the Axon Initial Segment2020

    • Author(s)
      Chowdhury Md. Imrul Hasan、Nishioka Tomoki、Mishima Noriko、Ohtsuka Toshihisa、Kaibuchi Kozo、Tsuboi Daisuke
    • Journal Title

      Cell Structure and Function

      Volume: 45 Issue: 2 Pages: 143-154

    • DOI

      10.1247/csf.20028

    • NAID

      130007894945

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Accumbal D2R-medium spiny neurons regulate aversive behaviors through PKA-Rap1 pathway.2020

    • Author(s)
      Lin, Y-H., Yamahashi, Y., Kuroda, K., Faruk M. O., Zhang, X., Yamada, K., Yamanaka, A., Nagai, T., Kaibuchi, K.
    • Journal Title

      Neurocham. Int.

      Volume: 143 Pages: 104935-104935

    • DOI

      10.1016/j.neuint.2020.104935

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Advances in defining signaling networks for the establishment of neuronal polarity2020

    • Author(s)
      Yasuhiro Funahashi, Takashi Watanabe, Kozo Kaibuchi
    • Journal Title

      Current Opinion in Cell Biology

      Volume: 63 Pages: 76-87

    • DOI

      10.1016/j.ceb.2019.12.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors2019

    • Author(s)
      Funahashi Yasuhiro、Ariza Anthony、Emi Ryosuke、Xu Yifan、Shan Wei、Suzuki Ko、Kozawa Sachi、Ahammad Rijwan Uddin、Wu Mengya、Takano Tetsuya、Yura Yoshimitsu、Kuroda Keisuke、Nagai Taku、Amano Mutsuki、Yamada Kiyofumi、Kaibuchi Kozo
    • Journal Title

      Cell Reports

      Volume: 29 Issue: 10 Pages: 3235-3252.e9

    • DOI

      10.1016/j.celrep.2019.10.116

    • NAID

      130007812598

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuronal Polarity: Positive and Negative Feedback Signals2019

    • Author(s)
      Tetsuya Takano, Yasuhiro Funahashi, Kozo Kaibuchi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 7 Pages: 69-69

    • DOI

      10.3389/fcell.2019.00069

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Identification of Protein Kinase Substrates by Kinase-Oriented Substrate Screening (KIOSS)2019

    • Author(s)
      Nishioka Tomoki、Amano Mutsuki、Funahashi Yasuhiro、Tsuboi Daisuke、Yamahashi Yukie、Kaibuchi Kozo
    • Journal Title

      Current Protocols in Chemical Biology

      Volume: 11 Issue: 1

    • DOI

      10.1002/cpch.60

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons2018

    • Author(s)
      Zhang XJ, Nagai T, Ahammad RU, Kuroda K, Nakamuta S, Nakano T, Yukinawa N, Funahashi Y, Yamahashi Y, Amano M, Yoshimoto J, Yamada K, and Kaibuchi K.
    • Journal Title

      Neurochemistry International

      Volume: 122 Pages: 8-18

    • DOI

      10.1016/j.neuint.2018.10.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive analysis of kinase-oriented phospho-signalling pathways2018

    • Author(s)
      Amano Mutsuki、Nishioka Tomoki、Tsuboi Daisuke、Kuroda Keisuke、Funahashi Yasuhiro、Yamahashi Yukie、Kaibuchi Kozo
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 4 Pages: 301-307

    • DOI

      10.1093/jb/mvy115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A FRET Biosensor for ROCK Based on a Consensus Substrate Sequence Identified by KISS Technology2017

    • Author(s)
      Chunjie Li, Ayako Imanishi, Naoki Komatsu, Kenta Terai, Mutsuki Amano, Kozo Kaibuchi and Michiyuki Matsuda
    • Journal Title

      Cell Structure and Function

      Volume: 42 Issue: 1 Pages: 1-13

    • DOI

      10.1247/csf.16016

    • NAID

      130005308480

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of long-range inhibitory signaling to ensure single axon formation2017

    • Author(s)
      Takano Tetsuya、Wu Mengya、Nakamuta Shinichi、Naoki Honda、Ishizawa Naruki、Namba Takashi、Watanabe Takashi、Xu Chundi、Hamaguchi Tomonari、Yura Yoshimitsu、Amano Mutsuki、Hahn Klaus M.、Kaibuchi Kozo
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 33-33

    • DOI

      10.1038/s41467-017-00044-2

    • NAID

      120006325188

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Phosphoproteomics of NMDA pathway leads to Rho-Kinase mediated synaptic plasticity through Shank3 phosphorylation.2020

    • Author(s)
      Rijwan Uddin Ahammad, Yasuhiro Funahashi, Xinjian Zhang, Emran Hossen, Md. Omar Faruk, Md Hasanuzzaman Shohag, Yifan Xu, Huanhuan Wang, Shinichi Nakamuta, Keisuke Kuroda, Daisuke Tsuboi, Tomoki Nishioka, Mutsuki Amano, Kozo Kaibuchi
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] MAPKによるNpas4リン酸化は報酬関連の遺伝子発現と行動を制御する2020

    • Author(s)
      船橋靖広、Anthony Ariza, 恵美亮佑、伊許凡、偉単、鈴木航、小澤祥、Rijwan Uddin Ahammad、 呉夢雅、高野哲也、由良義光、黒田啓介、永井拓、天野睦紀、山田清文、貝淵弘三
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] プロテインキナーゼAの抑制は、脳の報酬系に影響を与える2020

    • Author(s)
      許伊凡、船橋靖広、永井拓、貝淵弘三
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Phosphorylation of Npas4 by MAPK regulates reward-related gene expression and behaviors2020

    • Author(s)
      Yasuhiro Funahashi, Anthony Ariza, Ryosuke Emi, Yifan Xu, Shan Wei, Ko Suzuki, Sachi Kozawa, Rijwan Uddin Ahammad, Mengya Wu, Tetsuya Takano, Yoshimitsu Yura, Keisuke Kuroda, Taku Nagai, Mutsuki Amano, Kiyofumi Yamada、 Kozo Kaibuchi
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phosphoproteomics of NMDA pathway leads to Rho-Kinase mediated synaptic plasticity through Shank3 phosphorylation.2019

    • Author(s)
      Rijwan Uddin Ahammad, Yasuhiro Funahashi, Emran Hossen, Md. Omar Faruk, Md Hasanuzzaman Shohag, Sachi Kozawa, Hiroki Kato, Shinichi Nakamuta, Tomoki Nishioka, Daisuke Tsuboi, Mutsuki Amano, Kozo Kaibuchi
    • Organizer
      第71回日本細胞生物学会大会・第19回日本タンパク質科学学会年会 合同年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] KANPHOS Platform: A comprehensive database for kinase-associated neural phosphorylation signaling2019

    • Author(s)
      Mutsuki Amano, Tomoki Nishioka, Junichiro Yoshimoto, Takayuki Kannon, Shiro Usui, Kozo Kaibuchi
    • Organizer
      第71回日本細胞生物学会大会・第19回日本タンパク質科学学会年会 合同年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] An interactome-based proteomic approach for comprehensive substrate screening of protein kinases2019

    • Author(s)
      Mutsuki Amano, Kozo Kaibuchi
    • Organizer
      日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会 合同大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The mode of action of acetylcholine in nucleus accumbens that leads to aversive learning2019

    • Author(s)
      Yukie Yamahashi, Sho Iwanaga, Yuya Tokumoto, You-Hsin Lin, Xijian Zhang, Taku Nagai, Daisuke Tsuboi, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Suppressed dopamine release caused by aversive stimulus activates PKA-Rap1 signaling in accumbal D2R-medium spiny neuron2019

    • Author(s)
      You-Hsin Lin, Taku Nagai, Yukie Yamahashi, Keisuke Kuroda, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Discovery of a key missing signaling between RhoA/Rho-kinase and Ras during LTP2019

    • Author(s)
      Mengya Wu, Yasuhiro Funahashi, Tetsuya Takano, Daisuke Tsuboi, Rijwan Uddin Ahammad, Mutsuki Amano, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] KANPHOS (Kinase-Associated Phospho-Signaling) Platform - A comprehensive database for kinase-associated neural phosphorylation signaling"2019

    • Author(s)
      Keisuke Kuroda, Mutsuki Amano, Junichiro Yoshimoto, Taku Nagai, Takayuki Kannon, Tomoki Nishioka, Shiro Usui, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons2019

    • Author(s)
      Xinjian Zhang, Taku Nagai, Ahammad Rijwan Uddin, Keisuke Kuroda, Takashi Nakano, Junichiro Yoshimoto, Kiyofumi Yamada, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Phosphorylation of Npas4 by MAPK regulates reward-related gene expression and behaviors2019

    • Author(s)
      Yasuhiro Funahashi, Anthony Ariza, Ryosuke Emi, Yifan Xu, Shan Wei, Ko Suzuki, Sachi Kozawa, Tetsuya Takano, Yoshimitsu Yura, Keisuke Kuroda, Taku Nagai, Mutsuki Amano, Kiyofumi Yamada, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Molecular Mechanism of KCNQ Channels For Reward Behavior2019

    • Author(s)
      Daisuke Tsuboi, Tomoki Nishioka, Takushi Shimomura, Takeshi Otsuka, Yoshihiro Kubo, Yasuo Kawaguchi, Kozo Kaibuchi
    • Organizer
      Neuro2019 (第42回日本神経科学学会・ 第62回日本神経化学会大会合同大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Discovery of a key missing signaling between RhoA/Rho-kinase and Ras during LTP2019

    • Author(s)
      Mengya Wu, Yasuhiro Funahashi, Tetsuya Takano, Daisuke Tsuboi, Rijwan Uddin Ahammad, Mutsuki Amano, Kozo Kaibuchi
    • Organizer
      2019 ISN-ASN meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リン酸化から見た情動の分子基盤2019

    • Author(s)
      坪井大輔、林祐新、山橋幸恵、黒田啓介、貝淵弘三
    • Organizer
      第34回日本大脳基底核研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The mode of action of acetylcholine in nucleus accumbens that leads to aversive learning2019

    • Author(s)
      Yukie Yamahashi, Sho Iwanaga, Yuya Tokumoto, You-Hsin Lin, Xijian Zhang, Taku Nagai, Daisuke Tsuboi, Kozo Kaibuchi
    • Organizer
      第34回日本大脳基底核研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Dopamine and adenosine signaling pathways are analyzed in striatal medium spiny neurons using kinase-associated neural phospho-signaling (KANPHOS) database2019

    • Author(s)
      Xinjian Zhang, Taku Nagai, Keisuke Kuroda, Kozo Kaibuchi
    • Organizer
      Neuroscience2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MAPK ;mediated phosphorylation of MKL2 regulates nuclear localization and transcriptional activity in striatal neurons2019

    • Author(s)
      Anthony Ariza, Yasuhiro Funahashi , Kozo Kaibuchi
    • Organizer
      Neuroscience2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A new database for kinase-oriented phospho-proteomics:KANPHOS2018

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel dopamine receptor signaling in the striatum and its functional implications2018

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 名古屋大学大学院医学系研究科 神経情報薬理学講座HP

    • URL

      https://www.med.nagoya-u.ac.jp/Yakuri/papers/papers2020.htm

    • Related Report
      2020 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科 神経情報薬理学講座HP

    • URL

      https://www.med.nagoya-u.ac.jp/Yakuri/papers/papers2019.htm

    • Related Report
      2019 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科 神経情報薬理学講座HP

    • URL

      https://www.med.nagoya-u.ac.jp/Yakuri/index.htm

    • Related Report
      2018 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科 神経情報薬理学講座HP

    • URL

      https://www.med.nagoya-u.ac.jp/Yakuri/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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