Elucidation of molecular, physiological, and pathological functions of taste receptors expressed throughout the body

• Project/Area Number: 18K09523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Sanematsu Keisuke 九州大学, 歯学研究院, 講師 (70567502)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 味覚 / 味覚受容体 / 甘味 / Gタンパク質共役型受容体 / 甘味受容体 / 苦味受容体

Outline of Final Research Achievements

Our previous study suggests that the sweet receptor TAS1R2/TAS1R3 may alter the sensitivity to ligands under acidic conditions. Therefore, we tried to clarify how the sweet taste receptor changes their sensitivities due to pH changes. As a result, the artificial sweetener saccharin binds to the amino-terminal domain of hTAS1R2 as an agonist. At high concentrations, saccharin also binds to the transmembrane domain of hTAS1R3 as an antagonist. Under low pH conditions, our results suggest that saccharin stably binds to this domain to enhance the inhibitory effect.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、他のクラスC Gタンパク質共役型受容体の二量体構成に重要な知見を与える。また甘味受容体は環境pHによって感受性の制御を受ける可能性が示唆された。このことは酸味と甘味の相互作用が受容体レベルでも生じることを明らかにした。また、がん組織や炎症組織など、pHが下がる生態環境において、他のGタンパク質共役型受容体の感受性においても変化する可能性が示唆され、その機能制御にも重要な知見を与える。

Research Products

• [Int'l Joint Research] University of Illinois(米国)
• [Journal Article] Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice (2020)
  • Author(s): Osaki Ayana、Sanematsu Keisuke、Yamazoe Junichi、Hirose Fumie、Watanabe Yu、Kawabata Yuko、Oike Asami、Hirayama Ayaka、Yamada Yu、Iwata Shusuke、Takai Shingo、Wada Naohisa、Shigemura Noriatsu
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 23 Pages: 8958-8958
  • DOI: 10.3390/ijms21238958
  • Peer Reviewed / Open Access
• [Journal Article] Effects of insulin signaling on mouse taste cell proliferation (2019)
  • Author(s): Takai Shingo、Watanabe Yu、Sanematsu Keisuke、Yoshida Ryusuke、Margolskee Robert F.、Jiang Peihua、Atsuta Ikiru、Koyano Kiyoshi、Ninomiya Yuzo、Shigemura Noriatsu
  • Journal Title: PLOS ONE Volume: 14 Issue: 11 Pages: 1-16
  • DOI: 10.1371/journal.pone.0225190
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of Renin-Angiotensin System Components in the Taste Organ of Mice (2019)
  • Author(s): Shigemura Noriatsu、Takai Shingo、Hirose Fumie、Yoshida Ryusuke、Sanematsu Keisuke、Ninomiya Yuzo
  • Journal Title: Nutrients Volume: 11 Issue: 9 Pages: 2251-2251
  • DOI: 10.3390/nu11092251
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits (2019)
  • Author(s): Park Jihye、Selvam Balaji、Sanematsu Keisuke、Shigemura Noriatsu、Shukla Diwakar、Procko Erik
  • Journal Title: Journal of Biological Chemistry Volume: 294 Issue: 13 Pages: 4759-4774
  • DOI: 10.1074/jbc.ra118.006173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 味覚受容体再構築系におけるCa2+イメージングを用いた受容体機能解析 (2020)
  • Author(s): 實松 敬介， 重村 憲徳
  • Organizer: 第62回 歯科基礎医学会学術大会
• [Presentation] The effects of flecainide on taste bud organoid growth and behavioral sour taste response in mice. (2020)
  • Author(s): Kawabata Y, Takai S, Yoshida R, Sanematsu K, Kawabata F, Shigemura N.
  • Organizer: ISOT2020
• [Presentation] 甘味受容体感受性における低pHによる抑制効果の分子メカニズム (2020)
  • Author(s): 實松敬介、二ノ宮裕三、重村憲徳
  • Organizer: 第97回日本生理学会大会
  • Invited
• [Presentation] Molecular mechanisms of suppressing and modifying effects on sweet taste receptor sensitivity (2019)
  • Author(s): Keisuke Sanematsu, Yuzo Ninomiya, Noriatsu Shigemura
  • Organizer: ECRO 2019
  • Int'l Joint Research / Invited
• [Presentation] 低pH条件はサッカリンの甘味感受性を低下させる (2019)
  • Author(s): 實松敬介、尾崎礼奈、中林開人、重村憲徳
  • Organizer: 日本味と匂学会第53回大会
• [Presentation] Agonistic/antagonistic properties of sweet taste receptor (2018)
  • Author(s): Sanematsu K, Shigemura N, Ninomiya Y
  • Organizer: 第56回日本生物物理学会年会
  • Invited
• [Presentation] グルカゴン様ペプチド-１受容体遺伝子多型と甘味認知閾値との関連について (2018)
  • Author(s): 實松敬介, 井上真由子, 髙井信吾, 重村憲徳, 二ノ宮裕三
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] 實松敬介, 尾崎礼奈, 中林開人, 二ノ宮裕三, 重村憲徳 (2018)
  • Author(s): 低pH条件下における甘味受容体感受性の解析
  • Organizer: 日本味と匂学会第52回大会
• [Book] Clinical Neuroscience vol.37 no.12 1444-1447 (2019)
  • Author(s): 實松敬介、重村憲徳、二ノ宮裕三
  • Total Pages: 4
  • Publisher: 中外医学社