Analysis of novel C1q-family proteins that regulate functional synaptic circuits and memory.

• Project/Area Number: 26293042
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: KAKEGAWA WATARU 慶應義塾大学, 医学部, 准教授 (70383718)
• Co-Investigator(Kenkyū-buntansha): 鈴木 邦道 慶應義塾大学, 医学部, 研究員 (10713703) ; 竹尾 ゆかり 慶應義塾大学, 医学部, 研究員 (90624320)
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: シナプス / 小脳 / 運動記憶 / プルキンエ細胞 / 精神神経疾患 / 補体 / C1qファミリー / 記憶・学習 / シグナル伝達 / 神経科学

Outline of Final Research Achievements

It has been recently considered that synapses, which connect between neurons, are a basic element for the learning and memory. Therefore, to elucidate how synapses are formed and behave in vivo is a very important issue for understanding the process of learning and memory. In this study, we found that novel C1q-family proteins, which have a functional domain conserved in the C1q complement in immune system, regulate dynamically synapse morphology, functions and the localization of the synaptic proteins in the cerebellum and hippocampus (Elegheert, Kakegawa et al., Science, ’16; Matsuda et al., Neuron, ’16; Kakegawa et al., Neuron, ’15). Interestingly, as C1q-family proteins are widely expressed in various brain regions throughout life, our findings may provide useful information to understand general and novel mechanisms for the synaptic integrity in the CNS.

Research Products

• [Int'l Joint Research] University of Oxford/University of Cambridge(英国)
• [Int'l Joint Research] Vanderbilt University(米国)
• [Int'l Joint Research] Ｕｎｉｖｅｒｓｉｔｙ ｏｆ Ｏｘｆｏｒｄ(英国)
• [Journal Article] Chemical labelling for visualizing native AMPA receptors in live neurons. (2017)
  • Author(s): Wakayama, S., Kiyonaka, S., Arai, I., Kakegawa, W., Matsuda, S., Ibata, K., Nemoto, Y.L., Kusumi, A., Yuzaki, M., Hamachi, I.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 14850-14850
  • DOI: 10.1038/ncomms14850
  • NAID: 120006600363
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 Issue: 6296 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] Trans-synaptic modulation of kainate receptor functions by C1q-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: in press Issue: 4 Pages: 752-767
  • 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
• [Journal Article] Trans-synaptic modulation of kainite receptor functions by C1q-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, R.A., Yuzaki, M.
  • Journal Title: Neuron Volume: -
  • Peer Reviewed
• [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
• [Journal Article] RORalpha regulates multiple aspects of dendrite development in cerebellar Purkinje cells in vivo. (2015)
  • Author(s): Takeo, Y.H., Kakegawa, W., Miura, E., Yuzaki, M.
  • Journal Title: The Journal of Neuroscience Volume: 35 Issue: 36 Pages: 12518-12534
  • DOI: 10.1523/jneurosci.0075-15.2015
  • Peer Reviewed
• [Journal Article] 「強きをたすけ弱きをくじく」－シナプス刈り込みを担う新規C1ql1シグナリング. (2015)
  • Author(s): 掛川 渉, 柚﨑通介
  • Journal Title: 実験医学 （羊土社） Volume: 33 Pages: 1777-1780
• [Journal Article] GRAPHIC HOT PRESS－C1ql1: 脳内シナプスの形態と機能を制御する新しい分子. (2015)
  • Author(s): 掛川 渉, 柚﨑通介
  • Journal Title: 細胞工学 (学研メディカル秀潤社) Volume: 34 Pages: 692-693
• [Journal Article] Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. (2015)
  • Author(s): Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, Kohda K, Motohashi J, Takahashi A, Nagao S, Muramatsu SI, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M
  • Journal Title: Neuron Volume: 85 Issue: 2 Pages: 316-329
  • DOI: 10.1016/j.neuron.2014.12.020
  • Peer Reviewed / Open Access
• [Journal Article] 記憶・学習をささえる脳内D-アミノ酸の機能. (2015)
  • Author(s): 掛川 渉
  • Journal Title: D-アミノ酸学会誌 Volume: 3 Pages: 316-329
  • Acknowledgement Compliant
• [Journal Article] Cbln1 down-regulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells (2014)
  • Author(s): Ito-Ishida, A., Kakegawa, W., Kohda, K., Miura, E., Okabe, S. and M. Yuzaki
  • Journal Title: European Journal of Neuroscience Volume: 39 Issue: 8 Pages: 1268-80
  • DOI: 10.1111/ejn.12487
  • Peer Reviewed
• [Journal Article] Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum. (2014)
  • Author(s): Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Saruta C, Ishizaki Y, Yuzaki M, Kojima M, Furuichi T.
  • Journal Title: PLoS One. Volume: 9(6) Issue: 6 Pages: 1-10
  • DOI: 10.1371/journal.pone.0099524
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] D-アミノ酸の神経生理：脳内D-セリンによる記憶・学習制御. (2014)
  • Author(s): 掛川 渉, 柚﨑 通介
  • Journal Title: 生物工学会誌 Volume: 92 Pages: 657-660
• [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
• [Presentation] 分泌性補体ファミリー分子を介する小脳シナプス回路形成・機能制御. (2015)
  • Author(s): 掛川 渉
  • Organizer: 国立精神・神経医療研究センター 神経研究所 所内セミナー
  • Place of Presentation: 国立精神・神経医療研究センター（東京都小平市）
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] A novel mechanism underlying synaptic competition and maturation through C1q-family proteins. (2015)
  • Author(s): 掛川 渉, 柚﨑通介
  • Organizer: 第３８回日本神経科学学会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2015-07-30
  • Invited
• [Presentation] A novel mechanism underlying synaptic competition and maturation through C1q-family proteins (2015)
  • Author(s): 掛川 渉, 柚﨑 通介
  • Organizer: 第38回日本神経科学学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-30
• [Presentation] 新規免疫関連分子による小脳シナプス回路形成・機能制御機構 (2015)
  • Author(s): 掛川 渉
  • Organizer: 第49回慶應ニューロサイエンス研究会
  • Place of Presentation: 東京（信濃町）
  • Year and Date: 2015-03-21
• [Presentation] 新規免疫関連分子による小脳シナプス回路形成・制御機構の解明 (2015)
  • Author(s): 掛川 渉, 柚﨑 通介
  • Organizer: 東海大学/INCF Japan Node 小脳プラットフォーム合同神経科学ミニシンポジウム
  • Place of Presentation: 東京（高輪）
  • Year and Date: 2015-01-10
  • Invited
• [Presentation] D-SERINE CONTROLS LEARNING AND MEMORY THROUGH IONOTROPIC GLUTAMATE RECEPTORS (2014)
  • Author(s): 掛川 渉
  • Organizer: 第2回国際D-アミノ酸学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2014-09-03 – 2014-09-04
  • 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
• [Book] Physiological functions of D-serine mediated through delta2 glutamate receptors in the cerebellum. (2016)
  • Author(s): Kakegawa W, Yuzaki M.
  • Publisher: Springer Books
• [Book] Essentials of Cerebellum and Cerebellar Disorders: Long-term depression (2016)
  • Author(s): Kohda K, Kakegawa W, Yuzaki M.
  • Publisher: Springer Books
• [Book] Physiological functions of D-serine mediated through δ2 glutamate receptors in the cerebellum. (2015)
  • Author(s): Kakegawa, W., Yuzaki, M.
  • Publisher: Springer Books
• [Book] Long-Term Depression.-Essentials of Cerebellum and Cerebellar Disorders. (2015)
  • Author(s): Kohda, K., Kakegawa, W., Yuzaki, M.
  • 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/
• [Remarks] 柚﨑研究室HP
  • URL: http://www.yuzaki-lab.org/
• [Remarks] 柚﨑通介研究室HP
  • URL: http://www.yuzaki-lab.org/