A novel role of adhesion-GPCR in synaptic functions and motor learning.

• Project/Area Number: 16K15183
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: Kakegawa Wataru 慶應義塾大学, 医学部(信濃町), 准教授 (70383718)
• Co-Investigator(Renkei-kenkyūsha): Yuzaki Michisuke 慶應義塾大学, 医学部, 教授 (40365226) ; Miura Eriko 慶應義塾大学, 医学部, 研究員 (10571169) ; Motohashi Junko 慶應義塾大学, 医学部, 研究員 (10407083)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 細胞接着 / Gタンパク質共役型受容体 / シナプス / 記憶・学習 / Ｇタンパク質共役型受容体 / シグナル伝達 / 神経科学

Outline of Final Research Achievements

Recently, adhesion-type G protein-coupled receptors (ADGRs) have been intensively studied as molecules which regulate synapse integrity and learning & memory in the CNS. ADGR has a unique structure which contains an extracellular N-terminal domain with various types of functional domains, a seven-transmembrane region and an intracellular domain interacting with several signal molecules including G proteins. Despite its unique structure, the mechanisms by which ADGR behaves at synapses have remained unclear. In this study, we demonstrated that a brain-specific angiogenesis inhibitor 3 (BAI3), an ADGR member abundantly expressed at the synapses between climbing fiber (CF) and Purkinje cell in the cerebellum, plays crucial roles in synapse morphology, synaptic plasticity and cerebellar motor learning.

Research Products

• [Int'l Joint Research] University of Oxford/University of Cambridge(イギリス)
• [Int'l Joint Research] DZNE(ドイツ)
• [Int'l Joint Research] Montreal Clinical Research Institute(カナダ)
• [Int'l Joint Research] University of Oxford/University of Cambridge(イギリス)
• [Int'l Joint Research] Vanderbilt University(アメリカ)
• [Journal Article] 特集―スクラップ＆ビルドで発達する脳神経回路と高次脳機能：スクラップ＆ビルドによる小脳神経回路の動的制御. (2018)
  • Author(s): 掛川渉, 柚﨑通介
  • Journal Title: 実験医学 (羊土社) Volume: 印刷中
• [Journal Article] 記憶・学習の分子機構－そのときシナプスでは何が起きているのか？ (2018)
  • Author(s): 掛川渉, 柚﨑通介
  • Journal Title: BRAIN and NERVE－神経研究の進歩 (医学書院社) Volume: 印刷中
• [Journal Article] 脳神経機能における素過程・構造をコントロールする分子群－１７章 中枢神経系における分泌型シナプス形成因子. (2018)
  • Author(s): 松田恵子, 掛川渉, 柚﨑通介
  • Journal Title: 脳の分子論 (東京化学同人社) Volume: 印刷中
• [Journal Article] Chemical labeling for visualizing native AMPA receptors in live neurons (2017)
  • Author(s): Sho Wakayama, Shigeki Kiyonaka, Itaru Arai, Wataru Kakegawa, Shinji Matsuda, Keiji Ibata, Yuri L. Nemoto, Akihiro Kusumi, Michisuke Yuzaki & Itaru Hamachi
  • Journal Title: Nature Commun Volume: 印刷中 Pages: 14850-14850
  • DOI: 10.1038/ncomms14850
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 特集―ニューロリハビリテーションの進歩：中枢神経の可塑性とは. (2017)
  • Author(s): 河野まや, 掛川渉, 柚﨑通介
  • Journal Title: Clinical Neuroscience (中外医学社) Volume: 5 Pages: 523-527
• [Journal Article] Structural basis for integration of GluD receptors within synaptic organizer complexes. (2016)
  • Author(s): Elegheert, J., Kakegawa, W., Clay, E. J., Shanks, N., Behiels, E., Matsuda, K., Kohda, K., Miura, E., Rossmann, M., Mitakidis, N., Motohashi, J., Chang, T. V., Siebold, C., Greger, H. I., Nakagawa, T., K., Yuzaki, M., Aricescu, R.A.
  • Journal Title: Science Volume: 353 Pages: 295-299
  • DOI: 10.1126/science.aae0104
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Current Topics：シナプスに架かる記憶への架け橋：Neurexin-Cbln1-GluD2三者複合体構造. (2016)
  • Author(s): 掛川 渉, 柚﨑通介
  • Journal Title: 実験医学 (羊土社) Volume: 34 Pages: 3181-3184
• [Journal Article] Transsynaptic modulation of kainate receptor functions by Clq-like proteins. (2016)
  • Author(s): Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M, Watanabe I, Kano M, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M
  • Journal Title: Neuron Volume: 90 Pages: 752-67
  • DOI: 10.1016/j.neuron.2016.04.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 「補体ファミリー分子」とシナプス形成・維持. (2016)
  • Author(s): 掛川 渉, 松田恵子, 柚﨑通介
  • Journal Title: Annual Review神経2016 （中外医学社） Volume: - Pages: 35-43
• [Presentation] A novel D-serine signaling which underlies synaptic plasticity and motor learning in the cerebellum. (2017)
  • Author(s): Kakegawa, W., Yuzaki, M.
  • Organizer: 第３９回 日本生物学的精神医学会 (札幌)
  • Invited
• [Presentation] Synergistic action of two different GluD2 ligands on D-serine signaling in the cerebellum. (2017)
  • Author(s): Kakegawa, W.
  • Organizer: The 3rd International Conference of D-Amino Acid Research (Italy)
  • Int'l Joint Research / Invited
• [Presentation] シナプス分子群がもたらす運動記憶ダイナミズムの解明 (2016)
  • Author(s): 掛川 渉
  • Organizer: 次世代脳プロジェクト・若手シンポジウム
  • Place of Presentation: 一橋講堂 (東京都千代田区)
  • Invited
• [Book] D-Amino Acids: Physiology, Metabolism, and Application (2016)
  • Author(s): Kakegawa, W., Yuzaki, M.
  • Total Pages: 16
  • Publisher: Springer Books
• [Book] Essentials of cerebellum and cerebellar disorders (2016)
  • Author(s): Kohda, K., Kakegawa, W., Yuzaki, M.
  • Total Pages: 6
  • Publisher: Springer Books
• [Remarks] 慶應義塾大学医学部生理学教室 (柚﨑通介研究室)
  • URL: http://www.yuzaki-lab.org/