Sensing, processing and neurotransmission of taste in the taste buds

• Project/Area Number: 26713008
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: General physiology
• Research Institution: Kyoto 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), 講師 (20706824)
• Research Collaborator: Sun Hongxin ; Kashio Makiko ; Marunaka Yoshinori ; Miyazaki Hiroaki ; Niisato Naomi ; Nakajo Koichi ; Kido Mizuho ; Murakami Tatsuro ; Nambu Atsushi ; Kobayashi Kenta ; Sano Hiromi ; Matsumoto Ichiro ; Foskett J. Kevin ; Tordoff Michael G.
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
• Keywords: 味覚 / イオンチャネル / 神経伝達 / ATP / CALHM / 味蕾 / カルシウムイメージング / 生理学 / 感覚系 / 塩味 / GCaMP

Outline of Final Research Achievements

The sense of taste controls our eating behaviors. Full understanding of the taste mechanisms is invaluable for preventing lifestyle diseases such as diabetes and hypertension. We previously reported that CALHM1, a subunit of a voltage-gated plasma membrane ion channel, is an essential portion of the neurotransmitter release channel in taste bud cells. However, rigorous regulation of CALHM1 channel function by unknown mechanisms has been implicated in vivo. In this study, we discovered two regulatory mechanisms of CALHM1 channel: (1) CALHM1 gating and submembrane distribution is post-translationally regulated by S-palmitoylation, and (2) a CALHM1 paralog, CALHM3, forms a novel oligomeric ion channel with CALHM1 and the CALHM1/3 channel mediates neurotransmission of sweet, bitter, umami and amiloride-insensitive salt tastes.
These findings significantly advance our molecular understanding of taste mechanisms.

Research Products

• [Int'l Joint Research] ペンシルバニア大学/モネル化学感覚研究所/デラウェア大学(米国)
• [Int'l Joint Research] コペンハーゲン大学(デンマーク)
• [Journal Article] Adeno-Associated Virus-Mediated Gene Transferinto Taste Cells In Vivo (2017)
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Na+ homeostasis by epithelial Na+ channel (ENaC) and Nax channel (Nax): cooperation of ENaC and Nax. (2016)
  • Author(s): Marunaka, Y., Marunaka, R., Sun, H., Yamamoto, T., Kanamura, N. & Taruno, A..
  • Journal Title: Ann Transl Med. Volume: 4 Issue: S1 Pages: S11-S11
  • DOI: 10.21037/atm.2016.10.42
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Quercetin is a useful medicinal compound showing various actions including control of blood pressure, neurite elongation and epithelial ion transport. (2016)
  • Author(s): Marunaka, Y., Niisato, N., Miyazaki, H., Nakajima, K., Taruno, A., Sun, H., Marunaka, R., Okui., M., Yamamoto, T., Kanamura, N., Kogiso, H., Ikeuchi, Y., Kashio, M., Hosogi, S. & Nakahari, T.
  • Journal Title: Curr Med Chem. Volume: 23 Issue: 37 Pages: 1-12
  • DOI: 10.2174/0929867323666160919095043
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Calcium homeostasis modulator (CALHM) ion channels (2016)
  • Author(s): Ma Z, Tanis JE, Taruno A, Foskett JK
  • Journal Title: Pflugers Archiv - European Journal of Physiology Volume: 468(3) Issue: 3 Pages: 395-403
  • DOI: 10.1007/s00424-015-1757-6
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Simulation of Cl(-) Secretion in Epithelial Tissues: New Methodology Estimating Activity of Electro-Neutral Cl(-) Transporter. (2015)
  • Author(s): Sasamoto K, Niisato N, Taruno A, Marunaka Y.
  • Journal Title: Front Physiol Volume: 6 Pages: 370-370
  • DOI: 10.3389/fphys.2015.00370
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 分子レベルで明らかになってきた舌で甘さを感じるしくみ (2015)
  • Author(s): 樽野陽幸, 丸中良典
  • Journal Title: 砂糖類・でん粉情報 Volume: 1 Pages: 41-45
  • NAID: 40020321562
  • Open Access
• [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
• [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
• [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
• [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
• [Presentation] Homologous CALHM subunits assemble to form a novel voltage-gated ATP channel. (2016)
  • Author(s): 樽野陽幸, 宮崎裕明, 新里直美, 丸中良典
  • Organizer: ４大学連携フォーラム
  • Place of Presentation: 京都（京都薬科大学）
  • Year and Date: 2016-12-07
• [Presentation] 上皮細胞におけるCALHMチャネル極性ソーティングの分子基盤解析. (2016)
  • Author(s): 加塩麻紀子, 樽野陽幸, 丸中良典
  • Organizer: ４大学連携フォーラム
  • Place of Presentation: 京都（京都薬科大学）
  • Year and Date: 2016-12-07
• [Presentation] Current-direction/amplitude-dependent single channel gating kinetics of Pannexin 1 channel. (2016)
  • Author(s): 白石真土, 野村健, 樽野陽幸, 丸中良典
  • Organizer: ４大学連携フォーラム
  • Place of Presentation: 京都（京都薬科大学）
  • Year and Date: 2016-12-07
• [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
  • Year and Date: 2016-12-03
  • 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
  • Int'l Joint Research
• [Presentation] Homologous CALHM subunits assemble to form a novel voltage-gated ATP channel. (2016)
  • Author(s): Taruno A, Hiroaki Miyazaki, Naomi Niisato, Hongxin Sun, Makiko Kashio, 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
• [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
• [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
  • 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
  • Int'l Joint Research
• [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
  • 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, Hongxin Sun, Makiko Kashio, 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
• [Presentation] S-palmitoylation regulates calcium homeostasis modulator 1 ion channel (2016)
  • Author(s): Taruno A, Sun H, Kashio M, Marunaka Y
  • Organizer: 日本膜学会第３８年会
  • Place of Presentation: 早稲田大学西早稲田キャンパス63号館
  • Year and Date: 2016-05-10
• [Presentation] CALHM1 and CALHM3 are assembled 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93回日本生理学会大会
  • Place of Presentation: 札幌（札幌コンベンションセンター）
  • Year and Date: 2016-03-22
• [Presentation] N-linked glycosylation regulates CALHM1 channel function and subcellular localization (2016)
  • Author(s): Taruno A, Sun H, Kashio M, Marunaka Y
  • Organizer: 60th Annual Meeting of the Biophysical Society
  • Place of Presentation: Los Angeles, California (Loa Angeles Convention Center)
  • Year and Date: 2016-02-27
  • Int'l Joint Research
• [Presentation] CAL1APの同定とCALHM1/CAL1APチャネルの機能解析 (2015)
  • Author(s): Taruno A. Miyazaki H. Niisato N. Sun H. Kashio M. Marunaka Y
  • Organizer: 第１０８回近畿生理学談話会
  • Place of Presentation: 大阪（近畿大学）
  • Year and Date: 2015-10-24
• [Presentation] Cell type-specific recording of taste cell activity by genetically-encoded Ca2+ indicator (GECI) (2015)
  • Author(s): Taruno A, Marunaka Y
  • Organizer: 第49回日本味と匂学会大会
  • Place of Presentation: 岐阜（じゅうろくプラザ）
  • Year and Date: 2015-09-24
• [Presentation] Regulation of CALHM1 ion channel by N-linked glycosylation. (2015)
  • Author(s): Taruno A, Makiko Kashio, Hongxin Sun, Marunaka Y
  • Organizer: 第38回日本神経科学会大会
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-07-28
• [Presentation] 味覚神経伝達を担う新規形質膜ATP放出イオンチャネルCALHM1の同定と上皮細胞イオンチャネルの膜局在の数理モデル解析 (2015)
  • Author(s): Taruno A
  • Organizer: 日本膜学会第３７年会
  • Place of Presentation: 早稲田大学西早稲田キャンパス63号館
  • Year and Date: 2015-05-14
• [Presentation] Regulation of CALHM1 ion channel by N-linked glycosylation. (2015)
  • Author(s): Taruno, A. Kashio, M., Sun, H., & Marunaka, Y.
  • Organizer: 第92回日本生理学会大会.
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] CALHMイオンチャネルの構造・機能の解析. (2014)
  • Author(s): Taruno, A., Ma, Z., Niisato, N., Miyazaki, H., Kashio, M., Sun, H., Foskett, J.K., & Marunaka, Y.
  • Organizer: 膜シンポジウム2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-11-26 – 2014-11-27
• [Presentation] Identification of a novel ATP release ion channel, CALHM1, essentially required for purinergic neurotransmission of tastes. (2014)
  • Author(s): Taruno, A., Marunaka, Y., & Foskett, J.K.
  • Organizer: 上皮バリアと輸送についてのシンポジウム.
  • Place of Presentation: 草津
  • Year and Date: 2014-11-01 – 2014-11-02
• [Presentation] 味覚神経伝達を担う新規ATP放出イオンチャネルCALHM1の同定. (2014)
  • Author(s): Taruno A, Foskett JK, Marunaka Y.
  • Organizer: 生理学研究所研究会「粘膜免疫学と巻く輸送生理学の融合」.
  • Place of Presentation: 岡崎
  • Year and Date: 2014-10-27 – 2014-10-28
• [Presentation] CALHM1 channel mediation of purinergic neurotransmission from taste bud cells devoid of synapses. (2014)
  • Author(s): Taruno A, Foskett JK, Marunaka Y.
  • Organizer: 第37回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Remarks] 京都府立医科大学細胞生理学website
  • URL: http://kpum-molecular-cell-physiology.info