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Molecular basis underlying mechanoreception

Research Project

Project/Area Number 19H03329
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionAoyama Gakuin University

Principal Investigator

Hirata Hiromi  青山学院大学, 理工学部, 教授 (60402450)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords神経
Outline of Research at the Start

動物とは動く生物であり、外界の情報を感覚入力により認知し、行動という形で出力する。動物の感覚系としては五感が昔から知られているが、その1つである触覚は一次感覚ニューロンの末端が皮膚下に存在することが知られ、受容体分子も近年見つかりつつあるが、触覚受容や伝達の分子メカニズムには不明の点が多く残されている。本研究で研究代表者はゼブラフィッシュを動物モデルに、触刺激応答に異常のあるゼブラフィッシュ変異体を足がかりにして触覚に関わる分子を同定し、その分子機能をゼブラフィッシュを用いたin vivo解析および培養細胞を用いたin vitro解析で明らかにし、触覚受容や伝達の分子メカニズムの解明を目指す。

Outline of Final Research Achievements

Sensory neurons are responsible for tactile perception. But other than the PIEZO1 receptor, the molecular mechanism of tactile perception in vivo remains largely unclear. In this study, we employed zebrafish sensory motor system into tactile research and utilized zebrafish mutants with abnormal tactile sensation. We identified a number of genes required for tactile perception and clarified their roles in tactile reception. For example, we found that PIGK, one of the subunits of GPI transamidase enzyme, which is required for the biosynthesis of GPI-anchored proteins, contributes to tactile perception by regulating the axonal localization of voltage-gated sodium channels in primary sensory neurons. We also found that a variant of the PIGK gene caused neurodevelopmental disorders in humans.

Translated with DeepL.com (free version)

Academic Significance and Societal Importance of the Research Achievements

触覚研究の分野ではPIEZO1という受容体分子は同定されて研究が進展したが、PIEZO1のサブユニットや制御因子など、触覚に関連する分子基盤の知見は今でも少なく、不明の点が多く残されている。皮膚感覚の異常は不快感をまねき、生活の質を著しく低下させることから、触覚の理解はヒトが健康的な生活をおくるのに重要な要素である。本研究で触覚に必要であるとわかった遺伝子のヒトでのバリアントが神経発達障害を引き起こすこともわかり、触覚の研究が触覚分野にとどまらず、広く神経疾患の理解に寄与することが示されたと言える。

Report

(5 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (18 results)

All 2024 2023 2022 2021 2020

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (1 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Establishment of a zebrafish inbred strain, M-AB, capable of regular breeding and genetic manipulation2024

    • Author(s)
      Sadamitsu Kenichiro、Velilla Fabien、Shinya Minori、Kashima Makoto、Imai Yukiko、Kawasaki Toshihiro、Watai Kenta、Hosaka Miho、Hirata Hiromi、Sakai Noriyoshi
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-024-57699-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Congenital anaemia associated with loss-of-function variants in DNA polymerase epsilon 1.2024

    • Author(s)
      Takeuchi I, Tanase-Nakao K, Ogawa A, Sugawara T, Migita O, Kashima M, Yamazaki T, Iguchi A, Naiki Y, Uchiyama T, Tamaoki J, Maeda H, Shimizu H, Kawai T, Taniguchi K, Hirata H, Kobayashi M, Matsumoto K, Naruse K, Hata K, Akutsu H, Kato T, Narumi S, Arai K, Ishiguro A.
    • Journal Title

      J Med Genet.

      Volume: 61(3) Issue: 3 Pages: 239-243

    • DOI

      10.1136/jmg-2023-109444

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A resource of single‐cell gene expression profiles in a planarian <scp><i>Dugesia japonica</i></scp>2023

    • Author(s)
      Kashima Makoto、Komura Rei、Sato Yuki、Hashimoto Chikara、Hirata Hiromi
    • Journal Title

      Development, Growth &amp; Differentiation

      Volume: 66 Issue: 1 Pages: 43-55

    • DOI

      10.1111/dgd.12893

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of XBP1 but not ATF6α rescues heart failure induced by persistent ER stress in medaka fish2023

    • Author(s)
      Jin Byungseok、Ishikawa Tokiro、Kashima Makoto、Komura Rei、Hirata Hiromi、Okada Tetsuya、Mori Kazutoshi
    • Journal Title

      Life Science Alliance

      Volume: 6 Issue: 7 Pages: 1-20

    • DOI

      10.26508/lsa.202201771

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The p.Thr395Met missense variant of NFIA found in a patient with intellectual disability is a defective variant.2022

    • Author(s)
      Ogura Yurie、Uehara Tomoko、Ujibe Kota、Yoshihashi Hiroshi、Yamada Mamiko、Suzuki Hisato、Takenouchi Toshiki、Kosaki Kenjiro、Hirata Hiromi
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 188 Issue: 4 Pages: 1184-1192

    • DOI

      10.1002/ajmg.a.62638

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MED27, SLC6A7, and MPPE1 variants in a complex neurodevelopmental disorder with severe dystonia.2022

    • Author(s)
      Reid Kimberley M.、Spaull Robert、Salian Smrithi、Barwick Katy、Meyer Esther、Zhen Juan、Hirata Hiromi、et al.
    • Journal Title

      Movement Disorders

      Volume: 37 Issue: 10 Pages: 2139-2146

    • DOI

      10.1002/mds.29147

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DeLTa-Seq: direct-lysate targeted RNA-Seq from crude tissue lysate2022

    • Author(s)
      Kashima Makoto、Kamitani Mari、Nomura Yasuyuki、Mori-Moriyama Natsumi、Betsuyaku Shigeyuki、Hirata Hiromi、Nagano Atsushi J.
    • Journal Title

      Plant Methods

      Volume: 18 Issue: 1 Pages: 1-18

    • DOI

      10.1186/s13007-022-00930-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of zebrafish GABAA receptor subunits2021

    • Author(s)
      Sadamitsu Kenichiro、Shigemitsu Leona、Suzuki Marina、Ito Daishi、Kashima Makoto、Hirata Hiromi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-021-84646-3

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct-TRI: High-throughput RNA-extracting Method for all Stages of Zebrafish Development2021

    • Author(s)
      Ujibe Kota、Nishimura Kanako、Kashima Makoto、Hirata Hiromi
    • Journal Title

      BIO-PROTOCOL

      Volume: 11 Issue: 17 Pages: 1-10

    • DOI

      10.21769/bioprotoc.4136

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recurrent NFIA K125E substitution represents a loss-of-function allele: Sensitive in vitro and in vivo assays for nontruncating alleles2021

    • Author(s)
      Uehara Tomoko、Sanuki Rikako、Ogura Yurie、Yokoyama Atsushi、Yoshida Takeshi、Futagawa Hiroshi、Yoshihashi Hiroshi、Yamada Mamiko、Suzuki Hisato、Takenouchi Toshiki、Matsubara Kohei、Hirata Hiromi、Kosaki Kenjiro、Takano‐Shimizu Toshiyuki
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 185 Issue: 7 Pages: 2084-2093

    • DOI

      10.1002/ajmg.a.62226

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of αklotho causes reduced motor ability and short lifespan in zebrafish2021

    • Author(s)
      Ogura Yurie、Kaneko Ryoji、Ujibe Kota、Wakamatsu Yuma、Hirata Hiromi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-021-93909-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Reproducible Protocol to Measure the Critical Swimming Speed of Adult Zebrafish2020

    • Author(s)
      Wakamatsu Yuma、Kashima Makoto、Hirata Hiromi
    • Journal Title

      BIO-PROTOCOL

      Volume: 10 Issue: 16 Pages: 1-12

    • DOI

      10.21769/bioprotoc.3712

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the hypertension drug niflumic acid as a glycine receptor inhibitor2020

    • Author(s)
      Ito Daishi、Kawazoe Yoshinori、Sato Ayato、Uesugi Motonari、Hirata Hiromi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-8

    • DOI

      10.1038/s41598-020-70983-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA polymerase II subunit D is essential for zebrafish development2020

    • Author(s)
      Maeta Masanari、Kataoka Miku、Nishiya Yusuke、Ogino Kazutoyo、Kashima Makoto、Hirata Hiromi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-020-70110-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] InMeRF: prediction of pathogenicity of missense variants by individual modeling for each amino acid substitution2020

    • Author(s)
      Takeda Jun-ichi、Nanatsue Kentaro、Yamagishi Ryosuke、Ito Mikako、Haga Nobuhiko、Hirata Hiromi、Ogi Tomoo、Ohno Kinji
    • Journal Title

      NAR Genomics and Bioinformatics

      Volume: 2 Issue: 2 Pages: 1-11

    • DOI

      10.1093/nargab/lqaa038

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycine Receptor Autoantibodies Impair Receptor Function and Induce Motor Dysfunction2020

    • Author(s)
      Rauschenberger Vera、von Wardenburg Niels、Schaefer Natascha、Ogino Kazutoyo、Hirata Hiromi、Lillesaar Christina、Kluck Christoph J.、Meinck Hans‐Michael、Borrmann Marc、Weishaupt Andreas、Doppler Kathrin、Wickel Jonathan、Geis Christian、Sommer Claudia、Villmann Carmen
    • Journal Title

      Annals of Neurology

      Volume: 88 Issue: 3 Pages: 544-561

    • DOI

      10.1002/ana.25832

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ゼブラフィッシュが環境に適応して行動を変化させる分子メカニズム2020

    • Author(s)
      平田普三
    • Organizer
      日本動物学会第91回大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] ゼブラフィッシュ実験ガイド2020

    • Author(s)
      平田 普三
    • Total Pages
      148
    • Publisher
      朝倉書店
    • ISBN
      9784254171730
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2025-01-30  

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