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Neurotransmission of sensory information through CALHM ion channels

Research Project

Project/Area Number 16K15181
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Taruno Akiyuki  京都府立医科大学, 医学(系)研究科(研究院), 教授 (20706824)

Co-Investigator(Kenkyū-buntansha) 加塩 麻紀子  京都府立医科大学, 医学(系)研究科(研究院), 助教 (20631394)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsシナプス / イオンチャネル / CALHM / 味覚 / 神経伝達 / 翻訳後修飾 / 生理学 / 感覚系
Outline of Final Research Achievements

Using my original research tools, I analyzed function and expression of two ion channel subunits, CALHM1 and CALHM3. First, I discovered protein palmitoylation on CALHM1 regulating its gating and localization. Second, I identified a CALHM1/3 heteromer as the neurotransmitter-release pathway in taste receptor cells of the taste buds required for taste perception. Third, I elucidated the structure and localization of CALHM channel synapses in taste cells. Lastly, my analyses uncovered sensory cells expressing CALHM channel subunits.
These findings revealed the structure, localization, molecular mechanisms, function, and regulatory mechanisms of CALHM channel synapses of the taste buds, and further proposed novel physiological function of CALHM synapses.

Academic Significance and Societal Importance of the Research Achievements

細胞外ATPシグナルは味覚・機械・侵害など多くの感覚情報伝達など幅広い生理現象を担うが、多くの場合細胞からのATP放出の分子機構は不明である。本研究では味覚の認識を担う味蕾細胞からの神経伝達物質ATPの放出経路としてCALHM1/3チャネルを同定し、その機能調節機構も発見した。さらに、CALHMチャネルが担う味蕾細胞シナプスの構造とその形成原理の一端を明らかにすることで、シナプス小胞を持たない”イオンチャネルシナプス”とも呼ぶべき全く新しい化学シナプスの概念を確立した。さらにCALHMチャネルシナプスの新たな機能部位を示唆するデータを得たことは新たな学術領域の萌芽である。

Report

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

    (43 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 10 results,  Acknowledgement Compliant: 4 results) Presentation (22 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] ペンシルバニア大学/モネル化学感覚研究所/カリフォルニア大学アーバイン校(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ペンシルバニア大学/モネル化学感覚研究所(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] コペンハーゲン大学(デンマーク)

    • Related Report
      2017 Research-status Report
  • [Journal Article] CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane of epithelial cells including taste cells2019

    • Author(s)
      Kashio M, Wei-Qi G, Ohsaki Y, Kido MA, Taruno A
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2681-2681

    • DOI

      10.1038/s41598-019-39593-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AAV-Mediated Gene Delivery to Taste Cells of the Tongue2019

    • Author(s)
      Taruno A and Kashio M
    • Journal Title

      Methods in Molecular Biology

      Volume: 1950 Pages: 299-307

    • DOI

      10.1007/978-1-4939-9139-6_18

    • ISBN
      9781493991389, 9781493991396
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes2018

    • Author(s)
      Ma Zhongming、Taruno Akiyuki、Ohmoto Makoto、Jyotaki Masafumi、Lim Jason C.、Miyazaki Hiroaki、Niisato Naomi、Marunaka Yoshinori、Lee Robert J.、Hoff Henry、Payne Riley、Demuro Angelo、Parker Ian、Mitchell Claire H.、Henao-Mejia Jorge、Tanis Jessica E.、Matsumoto Ichiro、Tordoff Michael G.、Foskett J. Kevin
    • Journal Title

      Neuron

      Volume: 98 Issue: 3 Pages: 30249-30256

    • DOI

      10.1016/j.neuron.2018.03.043

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Innate and acquired tolerance to bitter stimuli in mice2018

    • Author(s)
      Mura Emi、Taruno Akiyuki、Yagi Minako、Yokota Kohei、Hayashi Yukako
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 12 Pages: e0210032-e0210032

    • DOI

      10.1371/journal.pone.0210032

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Action of Protein Tyrosine Kinase Inhibitors on the Hypotonicity-Stimulated Trafficking Kinetics of Epithelial Na<sup>+</sup> Channels (ENaC) in Renal Epithelial Cells: Analysis Using a Mathematical Model2018

    • Author(s)
      Marunaka Rie、Taruno Akiyuki、Yamamoto Toshiro、Kanamura Narisato、Marunaka Yoshinori
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 50 Issue: 1 Pages: 363-377

    • DOI

      10.1159/000494012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 塩味の受容とそのメカニズムについて2018

    • Author(s)
      樽野陽幸
    • Journal Title

      日本味と匂学会誌

      Volume: 25 Pages: 79-82

    • Related Report
      2018 Annual Research Report
  • [Journal Article] ATP Release Channels2018

    • Author(s)
      Taruno Akiyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 3 Pages: 808-808

    • DOI

      10.3390/ijms19030808

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The NOX1 isoform of NADPH oxidase is involved in dysfunction of liver sinusoids in nonalcoholic fatty liver disease.2018

    • Author(s)
      Matsumoto M, Zhang J, Zhang X, Liu J, Jiang JX, Yamaguchi K, Taruno A, Katsuyama M, Iwata K, Ibi M, Cui W, Matsuno K, Marunaka Y, Itoh Y, Torok NJ, Yabe-Nishimura C.
    • Journal Title

      Free Radic Biol Med.

      Volume: 115 Pages: 412-420

    • DOI

      10.1016/j.freeradbiomed.2017.12.019

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Post-translational palmitoylation controls the voltage gating and lipid raft association of the CALHM1 channel.2017

    • Author(s)
      Taruno A, Sun H, Nakajo K, Murakami T, Ohsaki Y, Kido MA, Ono F, Marunaka Y.
    • Journal Title

      Journal of Physiology

      Volume: 595 Issue: 18 Pages: 6121-6145

    • DOI

      10.1113/jp274164

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Current-direction/amplitude-dependent single channel gating kinetics of mouse pannexin 1 channel: a new concept for gating kinetics2017

    • Author(s)
      Nomura Takeshi、Taruno Akiyuki、Shiraishi Makoto、Nakahari Takashi、Inui Toshio、Sokabe Masahiro、Eaton Douglas C.、Marunaka Yoshinori
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 10512-10512

    • DOI

      10.1038/s41598-017-10921-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 甘味受容の仕組みと人工甘味料2017

    • Author(s)
      樽野陽幸
    • Journal Title

      食と医療

      Volume: 2 Pages: 40-46

    • Related Report
      2017 Research-status Report
  • [Journal Article] Adeno-Associated Virus-Mediated Gene Transferinto Taste Cells In Vivo2017

    • Author(s)
      Taruno A, Kashio M, Sun H, Kobayashi K, Sano H, Nambu A, Marunaka Y
    • Journal Title

      Chemical Senses

      Volume: 42 Pages: 69-78

    • DOI

      10.1093/chemse/bjw101

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hypotonicity activates a voltage-dependent membrane conductance in N2a neuroblastoma cells.2017

    • Author(s)
      Taruno, A. & Marunaka, Y.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 482 Issue: 2 Pages: 331-335

    • DOI

      10.1016/j.bbrc.2017.01.118

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Analysis of aprotinin, a protease inhibitor, action on the trafficking of epithelial Na+ channels (ENaC) in renal epithelial cells using a mathematical model.2017

    • Author(s)
      Sasamoto, K., Marunaka, R. #, Niisato, N., Sun, H., Taruno, A., Pezzotti, G., Yamamoto, T., Kanamura, N., Zhu, W., Nishio, K., Inui, T., Eaton, D.C., & Marunaka, Y.
    • Journal Title

      Cell Physiol Biochem

      Volume: 41 Issue: 5 Pages: 1865-1880

    • DOI

      10.1159/000471934

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Actions of quercetin, a polyphenol, on blood pressure.2017

    • Author(s)
      Marunaka, Y., Marunaka, R., Sun, H., Yamamoto, T., Kanamura, N., Inui, T. & Taruno, A.
    • Journal Title

      Molecules

      Volume: 22 Issue: 2 Pages: 209-209

    • DOI

      10.3390/molecules22020209

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Ion channel synapses of the taste bud2019

    • Author(s)
      Taruno A, Ma Z, Ohmoto M, Matsumoto I, Kido MA, Tordoff MG, Foskett JK
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies (FAOPS) Congress (in conjunction with the 96th Annual Meeting of the Physiological Society of Japan)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Taste cells lacking synapses open a wide pore channel for rapid neurotransmission of tastes2018

    • Author(s)
      Taruno A
    • Organizer
      第56回日本生物物理学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Ion channel synapse: CALHM1/3 channel mediates rapid neurotransmitter release in taste perception2018

    • Author(s)
      Taruno A
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 塩味の受容とそのメカニズムについて2018

    • Author(s)
      樽野陽幸
    • Organizer
      うま味研究会公開シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] CALHMs: Fast-activating voltage-gated ATP channels for rapid purinergic neurotransmission2018

    • Author(s)
      Taruno A, Ma Z, Ohmoto M, Matsumoto I, Kido MA, Tordoff MG, Foskett JK
    • Organizer
      The 49th National Institute of Physiological Sciences International Symposium “Ion channels: looking back, seeing ahead”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ion channel synapses of the taste bud2018

    • Author(s)
      Taruno A, Ma Z, Ohmoto M, Matsumoto I, Kido MA, Tordoff MG, Foskett JK
    • Organizer
      The 17th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ion channel synapses in taste buds2018

    • Author(s)
      Taruno A, Ma Z, Ohmoto M, Matsumoto I, Tordoff MG, Foskett JK
    • Organizer
      第52回日本味と匂学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] イオンチャネルから味覚へ(研究奨励賞受賞講演)2018

    • Author(s)
      樽野陽幸
    • Organizer
      第52回日本味と匂学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A CALHM1/CALHM3 heteromeric channel mediates purinergic neurotransmission of sweet, bitter, and umami tastes.2018

    • Author(s)
      Taruno A, Zhongming M, Ohmoto M, Matsumoto I, Tordoff MG, Foskett JK, Marunaka Y.
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Neurotransmission of taste mediated by calcium homeostasis modulator ion channels.2017

    • Author(s)
      樽野陽幸, 丸中良典
    • Organizer
      第94回日本生理学会大会.
    • Place of Presentation
      浜松(アクトシティ浜松)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Palmitoylation regulates gating and lipid raft association of CALHM1 channel.2017

    • Author(s)
      孫紅キン, 樽野陽幸, 中條浩一, 小野富三人, 丸中良典
    • Organizer
      第94回日本生理学会大会.
    • Place of Presentation
      浜松(アクトシティ浜松)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Molecular basis of polarized sorting of CALHM channels in epithelial cells.2017

    • Author(s)
      加塩麻紀子, 樽野陽幸, 丸中良典
    • Organizer
      第94回日本生理学会大会.
    • Place of Presentation
      浜松(アクトシティ浜松)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Current-direction/amplitude-dependent single channel gating kinetics of Pannexin 1 channel.2017

    • Author(s)
      白石真土, 野村健, 樽野陽幸, 丸中良典
    • Organizer
      第94回日本生理学会大会.
    • Place of Presentation
      浜松(アクトシティ浜松)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] CALHM channel-mediated neurotransmission of tastes.2017

    • Author(s)
      Taruno A
    • Organizer
      The 19th Scientific Meeting of the Australasian Association for ChemoSensory Science
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Palmitoylation of CALHM3 positively controls activity of the CALHM1/3 channel.2017

    • Author(s)
      奥井元貴, 孫紅昕, 樽野陽幸, 丸中良典
    • Organizer
      第110回近畿生理学談話会
    • Related Report
      2017 Research-status Report
  • [Presentation] パルミトイル化がCALHM1チャネルのゲーティングと脂質ラフト局在を制御する2017

    • Author(s)
      樽野陽幸、孫 紅昕 、中條浩一、村上達郎、大崎康吉、城戸瑞穂、小野富三人、丸中良典
    • Organizer
      日本味と匂学会第51回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Induction of foreign genes in taste cells in vivo.2016

    • Author(s)
      Taruno, A.
    • Organizer
      The 15th international symposium on molecular and neural mechanisms of taste and olfactory perception.
    • Place of Presentation
      福岡(九州大学)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular machinery for taste neurotransmission from the tongue to the brain.2016

    • Author(s)
      Taruno, A.
    • Organizer
      the 2nd UK-Japan Frontiers of Science Symposium.
    • Place of Presentation
      UK
    • Year and Date
      2016-11-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Homologous CALHM subunits assemble to form a novel voltage-gated ATP channel.2016

    • Author(s)
      Taruno A, Miyazaki H, Niisato N, Sun H, Kashio M, Marunaka Y.
    • Organizer
      第39回日本神経科学会大会.
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] Purinergic neurotransmission of taste by CALHM channel.2016

    • Author(s)
      Taruno A, Marunaka Y.
    • Organizer
      17th International Symposium on Olfaction and Taste.
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of CALHM1 channel by protein S-palmitoylation.2016

    • Author(s)
      Taruno A, Hongxin Sun, Makiko Kashio, Marunaka Y.
    • Organizer
      17th International Symposium on Olfaction and Taste.
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] S-パルミトイル化修飾によるCALHM1チャネル機能制御.2016

    • Author(s)
      Taruno A, Sun H, Kashio M, Marunaka Y.
    • Organizer
      日本膜学会第39年会.
    • Place of Presentation
      東京(早稲田大学)
    • Year and Date
      2016-05-10
    • Related Report
      2016 Research-status Report
  • [Book] 摂食と健康の科学2019

    • Author(s)
      樽野陽幸
    • Total Pages
      240
    • Publisher
      朝倉書店
    • Related Report
      2018 Annual Research Report
  • [Remarks] 樽野研究室ホームページ

    • URL

      https://www.tarunolab.com

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都府立医科大学細胞生理学website

    • URL

      http://kpum-molecular-cell-physiology.info

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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