Understanding of the purinergic signaling using spider toxins and insecticides

• Project/Area Number: 16K15180
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Kagawa University (2018); Osaka University (2016-2017)
• Principal Investigator: Fujiwara Yuichiro 香川大学, 医学部, 教授 (20532980)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ion channel / イオンチャネル / ATP受容体 / 生理学 / 薬理学

Outline of Final Research Achievements

Purinergic ATP receptor channels (P2X) are responsible for maintaining various physiological functions such as pain sensation and transmission, dilation of blood vessels and inflammatory reaction. These physiological functions are exhibited by membrane excitation and Ca2+ dependent cellular reactions through P2X. In this study we explored the molecular basis of ion selectivity and its physiological roles using blockers and activators of P2X.

Academic Significance and Societal Importance of the Research Achievements

ATP受容体のP2Xは、痛みの受容と伝達、血管の拡張、炎症反応など様々な生理機能に関係している。これら生理機能はP2Xから流入する陽イオンによる膜の興奮やCa2+による細胞内応答により発揮される。本研究により、P2Xのイオンの透過性の分子基盤とその生理機能が明らかになったことにより、将来的には、新しいタイプの鎮痛薬や抗高血圧薬への開発が期待される。

Research Products

• [Journal Article] Structural Basis for the Membrane Association of Ankyrin (2018)
  • Author(s): 藤原 祐一郎, 近藤 寛子, 城田 松之, 木下 賢吾
  • Journal Title: Seibutsu Butsuri Volume: 58 Issue: 3 Pages: 152-154
  • DOI: 10.2142/biophys.58.152
  • NAID: 130007378614
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed / Open Access
• [Journal Article] Temperature-Sensitive Gating of Voltage-Gated H+ Channels (2017)
  • Author(s): Fujiwara Y.
  • Journal Title: Journal of Physiological Sciences, Supplement1 Volume: 67
  • Peer Reviewed
• [Journal Article] A study of dynamics of palmitoylated Ankyrin-G around a lipid bilayer by coarse-grained simulations (2017)
  • Author(s): Kondo XH, Fujiwara Y., Shirota M., Kinoshita K.
  • Journal Title: Journal of Physiological Sciences, Supplement1 Volume: 67
  • Peer Reviewed
• [Journal Article] Structural insights into the nucleotide base specificity of P2X receptors. (2017)
  • Author(s): Kasuya G, Fujiwara Y, Tsukamoto H, Morinaga S, Ryu S, Touhara K, Ishitani R, Furutani Y, Hattori M, Nureki O.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 45208-45208
  • DOI: 10.1038/srep45208
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Conductance of P2X4 receptor is determined by conformational equilibrium in the transmembrane region (2016)
  • Author(s): Minato Y, Suzuki S , Hara T, Kofuku Y, Kasuya G, Fujiwara Y, Igarashi S, Suzuki E, Nureki O, Hattori M, Ueda T, Shimada I
  • Journal Title: Proc. Natl. Acad. Sci. Volume: 発行中 Issue: 17 Pages: 4741-4746
  • DOI: 10.1073/pnas.1600519113
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison between mouse and sea urchin orthologs of voltage-gated proton channel suggests role of S3 segment in activation gating (2016)
  • Author(s): Sakata S, Miyawaki N, McCormack TJ, Arima H, Kawanabe A, Ozkucur N, Kurokawa T, Jinno Y, Fujiwara Y, Okamura Y
  • Journal Title: Biochem. Biophys. Acta. Volume: 1858 Issue: 12 Pages: 2972-2983
  • DOI: 10.1016/j.bbamem.2016.09.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Crystal structures of the TRIC trimeric intracellular cation channel orthologues. (2016)
  • Author(s): Kasuya G, Hiraizumi M, Maturana AD, Kumazaki K, Fujiwara Y, Liu K, Nakada-Nakura Y, Iwata S, Tsukada K, Komori T, Uemura S, Goto Y, Nakane T, Takemoto M, Kato HE, Yamashita K, Wada M, Ito K, Ishitani R, Hattori M, Nureki O.
  • Journal Title: Cell Res. Volume: 26 Issue: 12 Pages: 1288-1301
  • DOI: 10.1038/cr.2016.140
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural basis for the membrane association of ankyrinG via palmitoylation (2016)
  • Author(s): Fujiwara Y, Kondo H, Shirota M, Kobayashi M, Takeshita K, Nakagawa A, Okamura Y, Kinoshita K
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 23981-23981
  • DOI: 10.1038/srep23981
  • Peer Reviewed / Open Access
• [Presentation] What is the pH-gradient Sensing in the Voltage- Gated H+ Channel? (2019)
  • Author(s): 藤原祐一郎
  • Organizer: 第9回アジアオセアニア生理学会（第96回日本生理学会合同大会）
  • Int'l Joint Research
• [Presentation] Toward the understanding of hexose specificity of Na+ D-glucose cotransporters SGLT1 and SGLT2 (2019)
  • Author(s): 神鳥和代、藤原祐一郎
  • Organizer: 第9回アジアオセアニア生理学会（第96回日本生理学会合同大会）
  • Int'l Joint Research
• [Presentation] Ion Permeation of Voltage Sensor and its Foundation Structure (2019)
  • Author(s): 片木絢子、藤原祐一郎
  • Organizer: 第9回アジアオセアニア生理学会（第96回日本生理学会合同大会）
  • Int'l Joint Research
• [Presentation] 電位依存性Ｈ+チャネルの電気的・化学的勾配センシング機構 (2018)
  • Author(s): 藤原祐一郎
  • Organizer: 蛋白研研究会「構造情報に基づいた膜イオン輸送タンパク質の 生理機能の解明に向けて」
  • Invited
• [Presentation] Approaches to structural dynamics of the voltage-gated H+ channel gating. (2018)
  • Author(s): 藤原祐一郎
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] 電気生理で蛋白質を解析する (2017)
  • Author(s): 藤原祐一郎
  • Organizer: 第66回NCVC研究者交流会
  • Invited
• [Presentation] 電位依存性プロトンチャネルの温度感受性ゲーティング (2017)
  • Author(s): 藤原祐一郎
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Invited
• [Presentation] 粗視化シミュレーションによるアンキリンGの細胞膜周辺での動態の解析 (2017)
  • Author(s): 近藤寛子、藤原祐一郎、城田松之、木下 賢吾
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Invited
• [Presentation] 電位依存性H+チャネルのゲーティングとその構造基盤 (2017)
  • Author(s): 藤原祐一郎
  • Organizer: Advanced Biological Chemistry Seminar 2017
  • Place of Presentation: 京都
  • Invited
• [Remarks] 温度生物学トピックス「TRPV1の熱活性はポアドメインに備わっている。」
  • URL: http://www.nips.ac.jp/thermalbio/report/report2018_01.html