Regulation of synaptic plasticity via hetero-GPCR modulation: an analysis using surface plasmon resonance imaging

• Project/Area Number: 26430012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: University of Toyama
• Principal Investigator: Tabata Toshihide 富山大学, 大学院理工学研究部(工学), 教授 (80303270)
• Co-Investigator(Renkei-kenkyūsha): SHINOHARA Hiroaki 富山大学, 大学院理工学研究部(工学), 教授 (60178887) ; KAMIKUBO Yuji 順天堂大学, 医学部, 助教 (80509670)
• Research Collaborator: YOKOYAMA Tomoki ; FUKUSHIMA Toshiki
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: Gタンパク質共役型受受容体 / ニューロン / シナプス可塑性 / グルタミン酸 / ガンマ・アミノ酪酸 / Cキナーゼ / Gタンパク質共役型受容体 / 蛍光カルシウム・イメージング / アデノシン / 表面プラズモン共鳴

Outline of Final Research Achievements

In cerebellar Purkinje cells, type-1 metabotropic glutamate receptor (mGluR1), which serves as the trigger of synaptic plasticity underlying motor learning, is suggested to be complexed with adenosine A1 receptor (A1R) and B-type gamma-aminobutyric acid receptor (GABAbR). We applied surface plasmon resonance imaging and fluorometry to HEK-293 cells heterologously expressing these receptors and found that A1R and GABAbR can form complexes with mGluR1 and modulate mGluR1 signaling without the neuron-specific cellular environment. We also found that these modulations do not require Gi/o protein and may be induced dynamically with cerebrospinal fluid levels of adenosine and GABA. These findings provide an insight into the regulatory mechanism of cerebellar motor learning.

Research Products

• [Journal Article] A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and left ventricular noncompaction (2018)
  • Author(s): R. Yokoyama, K. Kinoshita, Y. Hata, M. Abe, K. Matsuoka, K. Hirono, M. Kano, M. Nakazawa, F. Ichida, N. Nishida, T. Tabata
  • Journal Title: Heart and Vessels Volume: 印刷中 Issue: 7 Pages: 802-819
  • DOI: 10.1007/s00380-018-1116-6
  • Peer Reviewed
• [Journal Article] アデノシン受容体の神経系における機能と役割 (2017)
  • Author(s): 田端俊英、 上窪裕二
  • Journal Title: Clinical Neuroscience Volume: 35 Pages: 10-11
• [Journal Article] アデノシン受容体をターゲットとした臨床応用と最新研究 (2017)
  • Author(s): 上窪裕二、田端俊英
  • Journal Title: Clinical Neuroscience Volume: 35 Pages: 128-129
• [Journal Article] Application of surface plasmon resonance imaging to monitoring G protein-coupled receptor signaling and its modulation in a heterologous expression system (2016)
  • Author(s): Yuki Nonobe, Tomoki Yokoyama, Yuji Kamikubo, Sho Yoshida, Nozomi Hisajima, Hiroaki Shinohara, Yuki Shiraishi, Takashi Sakurai and Toshihide Tabata
  • Journal Title: BMC Biotechnology Volume: 16：36 Issue: 1 Pages: 1-9
  • DOI: 10.1186/s12896-016-0266-9
  • Peer Reviewed / Open Access
• [Journal Article] SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel (2016)
  • Author(s): Kinoshita K, Takahashi H, Hata Y, Nishide K, Kato M, Fujita H, Yoshida S, Murai K, Mizumaki K, Nishida K, Yamaguchi Y, Kano M, Tabata T, Nishida N
  • Journal Title: Heart Rhythm Volume: 13 Issue: 5 Pages: 1113-1120
  • DOI: 10.1016/j.hrthm.2016.01.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] アデノシン受容体の種類とあらまし (2016)
  • Author(s): 田端俊英、 上窪裕二
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 1288-1289
• [Journal Article] グループII型およびIII型代謝型グルタミン酸受容体の生理的および薬理的作用 (2016)
  • Author(s): 上窪裕二, 田端俊英
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 256-257
• [Journal Article] グループI型代謝型グルタミン酸受容体の生理的および薬理的作用 (2016)
  • Author(s): 上窪裕二, 田端俊英
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 136-137
• [Journal Article] 代謝型グルタミン酸受容体の構造と種類 (2016)
  • Author(s): 上窪裕二, 田端俊英
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 8-9
• [Journal Article] Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor (2015)
  • Author(s): Kamikubo Y, Tabata T, Sakairi H, Hashimoto Y, Sakurai T
  • Journal Title: Journal of Pharmacological Sciences Volume: 128 Issue: 3 Pages: 125-130
  • DOI: 10.1016/j.jphs.2015.06.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Susceptibilities of Human Ether-à-Go-Go-Related Gene Channel with the G487R Mutation to Arrhythmogenic Factors (2015)
  • Author(s): Hisajima N, Hata Y, Kinoshita K, Fukushima T, Nishida N, Kano M, Tabata T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 5 Pages: 781-784
  • DOI: 10.1248/bpb.b14-00630
  • NAID: 130005068093
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line. (2014)
  • Author(s): Ayako Kumagai, Akira Fujita, Tomoki Yokoyama, Yuki Nonobe, Yasuhiro Hasaba, Tsutomu Sasaki, Yumi Itoh, Minako Koura, Osamu Suzuki, Shigeki Adachi, Haruko Ryo, Arihiro Kohara, Lokesh P. Tripathi, Masato Sanosaka, Toshiki Fukushima, Taisei Nomura, Hiroshi Takemori, et al.
  • Journal Title: Genes Volume: 5 Issue: 4 Pages: 1095-1114
  • DOI: 10.3390/genes5041095
  • Peer Reviewed / Open Access
• [Journal Article] A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction. (2014)
  • Author(s): Kinoshita K, Komatsu T, Nishide K, Hata Y, Hisajima N, Takahashi H, Kimoto K, Aonuma K, Tushima E, Tabata T, Yoshida T, Mori H, Nishida K, Yamaguchi Y, Ichida F, Fukurotani K, Inoue H, Nishida N.
  • Journal Title: J Mol Cell Cardiol Volume: 72 Pages: 273-280
  • DOI: 10.1016/j.yjmcc.2014.03.019
  • Peer Reviewed / Open Access
• [Journal Article] Modification of <i>KCNH2</i>-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism (2014)
  • Author(s): Tabata T, Yamaguchi Y, Hata Y, Ichida F, Mori H
  • Journal Title: Circulation Journal Volume: 78 Issue: 9 Pages: 2331
  • DOI: 10.1253/circj.CJ-14-0654
  • NAID: 130004427967
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Presentation] Signal crosstalk and complex formation of mGluR1 and GABAbR (2018)
  • Author(s): Y. Kamikubo, H. Sakairi, T. Tabata, T. Sakurai
  • Organizer: 日本生理学会大会
• [Presentation] Regulation of type-1 metabotropic glutamate receptors function through inter-GPCR interplay (2017)
  • Author(s): Y. Kamikubo, H. Sakairi, M. Abe, K. Matsuoka, T. Tabata, T. Sakurai
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] Complex formation and functional interaction between mGluR1 and GABAbR in a heterologous expression system (2017)
  • Author(s): K. Matsuoka, M. Abe, H. Sakairi, Y. Kamikubo, T. Sakurai, T. Tabata
  • Organizer: 日本神経科学大会
• [Presentation] Modulation of type-1 metabotropic glutamate receptor by adenosine A1 receptor: an analysis with surface plasmon resonance imaging (2016)
  • Author(s): S. Yoshida, Y. Kamikubo, H. Shinohara, Y. Shiraishi, T. Sakurai, T. Tabata
  • Organizer: 日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] A novel HCN4 mutation in a patient with left ventricular noncompaction impairs the pacemaker current (2016)
  • Author(s): Kinoshita K, Yokoyama R, Takahashi Y, Hata Y, Tabata T, Hirono K, Ichida F, Nishida N
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18
• [Presentation] Bidirectional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor (2015)
  • Author(s): Kamikubo Y, Tabata T, Sakairi H, Hashimoto Y, Sakurai T
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] T-588 analog TK-6 impairs the hippocampus-dependent trace eyeblink conditioning in mice (2015)
  • Author(s): Ota M, Ishikawa M, Tanaka K, Kitagawa H, Usui K, Kohno T, Okada T, Minehira D, Toyooka N, Tabata T, Kawahara S
  • Organizer: 日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Electrophysiological characterization of a novel SCN5A mutant identified in a Brugada syndrome patient (2015)
  • Author(s): Takahashi H, Kinoshita K, Yoshida S, Fujita H, Murai K, Tabata T
  • Organizer: 日本生理学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] アデノシンA1受容体と代謝型グルタミン酸受容体の複合体形成と機能的相互作用 (2014)
  • Author(s): 上窪裕二, 坂入伯駿, 田端俊英, 櫻井隆
  • Organizer: 日本薬理学会関東部会
  • Place of Presentation: 横浜
  • Year and Date: 2014-10-11
• [Presentation] GRID2はメマンチンの作用機序における新しい調節因子である (2014)
  • Author(s): 熊谷彩子, 伊東祐美, 賀川舞, 松田潤一郎, 佐々木勉, 田端俊英, 竹森洋
  • Organizer: 日本臨床分子医学会大会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-11 – 2014-04-12
• [Remarks] 富山大学大学院理工学研究部生体情報処理研究室ホームページ
  • URL: http://www3.u-toyama.ac.jp/biophys/index.html
• [Remarks] 富山大学大学院理工学研究部神経情報工学研究室ホームページ
  • URL: https://niteut.eng.u-toyama.ac.jp/Lab_NIT/Intro_ai_za.html
• [Remarks] 富山大学大学院理工学研究部（工学）知能情報工学専攻 田端チーム ホームページ
  • URL: https://niteut.eng.u-toyama.ac.jp/Lab_NIT/Intro_ai_za.html
• [Remarks] 富山大学大学院理工学研究部（工学領域）知能情報工学専攻神経情報工学研究室ホームページ
  • URL: http://niteut.eng.u-toyama.ac.jp/Lab_NIT/Intro_ai_za.html