The molecular mechanism of synapse organization and modulation via C1q family proteins

• Project/Area Number: 26430023
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Keio University
• Principal Investigator: Matsuda Keiko 慶應義塾大学, 医学部(信濃町), 講師 (40383765)
• Co-Investigator(Renkei-kenkyūsha): Budisantoso Timotheus 慶應義塾大学, 医学部, 助教 (70724681)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: シナプス / グルタミン酸受容体 / 補体 / 海馬 / 補体分子 / ｼﾅﾌﾟｽ / ｸﾞﾙﾀﾐﾝ酸受容体 / カイニン酸 / 苔状線維 / CA3 / シナプス形成 / シナプス伝達 / C1q

Outline of Final Research Achievements

Kainate-type ionotropic glutamate receptors (KARs) are highly expressed at synapses between mossy fibers (MFs) and CA3 pyramidal neurons in the hippocampus and important modulators of neural circuit activities. Although diverse KAR roles depend on their subcellular localization, how they are targeted to specific sites is currently unknown. We have demonstarated that the C1q-like proteins C1ql2 and C1ql3, produced by MFs, interact with the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits to determine location and function of KARs. In C1ql2/3-double null mice, CA3 synaptic responses lost the slow, KAR-mediated, components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3-double null mice, leading to reduced recurrent circuit activities. C1q-family proteins, broadly expressed, are likely to modulate KAR function throughout the brain.

Research Products

• [Int'l Joint Research] Division of Structural Biology/Wellcome Trust Centre for Human Genetics/University of Oxford(英国)
• [Int'l Joint Research] University of Oxford(英国)
• [Journal Article] Synapse organization and modulation through C1q family (2017)
  • Author(s): Matsuda K.
  • Journal Title: Neuroscience Research Volume: 116 Pages: 46-53
  • DOI: 10.1016/j.neures.2016.11.004
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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] 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] Enriched Expression of GluD1 in Higher Brain Regions and Its Involvement in Parallel Fiber-Interneuron Synapse Formation in the Cerebellum. (2014)
  • Author(s): Konno K, Matsuda K, Nakamoto C, Uchigashima M, Miyazaki T, Yamasaki M, Sakimura K, Yuzaki M, Watanabe M.
  • Journal Title: J Neurosci. Volume: 34 Pages: 7412-7424
  • NAID: 120005537463
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Synapse organization and modulation via C1q family proteins and their receptors (2017)
  • Author(s): Matsuda K. and Yuzaki M.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] Trans-synaptic modulation of hippocampal CA3 neurons through mossy fiber derived-secreted molecules, C1ql2 and C1ql3 (2016)
  • Author(s): Matsuda K. and Yuzaki M.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-07-20
• [Presentation] Synapse organization and regulation through novel type of complement C1q family (2015)
  • Author(s): Keiko Matsuda, Michisuke Yuzaki
  • Organizer: 第38回日本神経科学会
  • 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] Synapse organization and regulation through novel type of complement C1q family (2015)
  • Author(s): Matsuda K, Bidisantoso T, Yuzaki M
  • Organizer: 第38回 日本神経科学大会 - 日本神経科学学会
  • Place of Presentation: 神戸国際会議場,兵庫
  • Year and Date: 2015-07-28 – 2015-07-31
• [Presentation] Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum (2014)
  • Author(s): Konno K, Matsuda K, Nakamoto C, Sakimura K, Yuzaki M, Watanabe M.
  • Organizer: 北米神経科学会
  • Place of Presentation: ワシントンDC,USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Book] 『脳の分子論（仮題）』 17章 中枢神経系における分泌型シナプス形成因子 (2016)
  • Author(s): 松田恵子 掛川渉 柚崎通介
  • Publisher: 化学同人
• [Book] Annual Review神経2016 項目：「補体C1q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 柚崎通介
  • Publisher: 中外医学社
• [Remarks] Yuzaki lab. Publication
  • URL: http://www.yuzaki-lab.org/publication/2016-2