Synapse formation and maintenance in adult brain : characterization of a new anterograde signal

• Project/Area Number: 19200026
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Keio University
• Principal Investigator: YUZAKI Michisuke Keio University, 医学部, 教授 (40365226)
• Co-Investigator(Kenkyū-buntansha): KOHDA Kazuhisa 慶應義塾大学, 医学部, 講師 (40334388) ; KAKEGAWA Wataru 慶應義塾大学, 医学部, 助教 (70383718)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥49,270,000 (Direct Cost: ¥37,900,000、Indirect Cost: ¥11,370,000); Fiscal Year 2010: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2009: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2007: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
• Keywords: シナプス形成 / 記憶 / 長期抑圧 / 小脳 / シナプス可塑性 / グルタミン酸受容体 / 可塑性 / プルキンエ細胞 / 分子 / 細胞神経科学 / トランスジェニックマウス

Research Abstract

Memories are believed to be stored as functional and morphological changes at synapses. To understand the underlying molecular mechanisms, we focused on two molecules, the δ2 glutamate receptor and Cbln1, which play essential roles in cerebellar functions, including motor memory. We found that Cbln1, released from cerebellar granule cells, binds directly to the amino terminus of the δ2 receptor and regulate synapse formation. Furthermore, the carboxyl terminus of the δ2 receptor regulates induction of functional synaptic plasticity.

Research Products

• [Journal Article] A new rapid protocol for eyeblink conditioning to assess cerebellar motor learning. (2011)
  • Author(s): Emi, K., Kohda, K., Kakegawa, W., Narumi, S., Yuzaki, M
  • Journal Title: Neurochem.Res. (in press)
• [Journal Article] Cbln1 and the Delta2 Glutamate Receptor-An Orphan Ligand and an Orphan Receptor Find Their Partners (2011)
  • Author(s): Matsuda K, Yuzaki M
  • Journal Title: Cerebellum (in press)
• [Journal Article] Cbln1 and its family proteins in synapse formation and maintenance. (2011)
  • Author(s): Yuzaki M
  • Journal Title: Curr Opin Neurobiol 21 Pages: 215-220
• [Journal Article] Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. (2011)
  • Author(s): Matsuda, K., Yuzaki, M.
  • Journal Title: Eur.J.Neurosci Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Cbln1 and the Delta2 Glutamate Receptor-An Orphan Ligand and an Orphan Receptor Find Their Partners. (2011)
  • Author(s): Matsuda, K., Yuzaki, M.
  • Journal Title: Cerebellum Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Cbln1 is a ligand for an orphan glutamate receptor ・2, a bidirectional synapse organizer. (2010)
  • Author(s): Matsuda K, Miura E, Miyzaki T, Kakegawa, W, Emi K, Narumi S, Fukazawa Y, Ito-Ishida A, Kondo T, Shigemoto R, Watanabe M, Yuzaki M
  • Journal Title: Science 328 Pages: 363-368
• [Journal Article] Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins. (2010)
  • Author(s): Iijima T, Miura E, Watanabe M, Yuzaki M
  • Journal Title: Eur J Neurosci 31 Pages: 1606-1615
• [Journal Article] Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers. (In: Special Issue : Formation, Regulation & Plasticity of Glutamatergic Synapse). (2010)
  • Author(s): Yuzaki M
  • Journal Title: Eur J Neurosci 32 Pages: 191-197
• [Journal Article] Cbln1 is a ligand for an orphan glutamate receptor □2, a bidirectional synapse organizer. (2010)
  • Author(s): Matsuda, K., Miura, E., Miyzaki, T., Kakegawa, W, Emi, K., Narumi, S., Fukazawa, Y., Ito-Ishida, A., Kondo, T., Shigemoto, R., Watanabe, M., Yuzaki.M
  • Journal Title: Science Volume: 328 Pages: 363-368
  • Peer Reviewed
• [Journal Article] Distinct expression of Clq-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins. (2010)
  • Author(s): Iijima, T., Miura, E., Watanabe, M., Yuzaki M.
  • Journal Title: Eur J Neurosci Volume: 31 Pages: 1606-1615
  • Peer Reviewed
• [Journal Article] Cbln1 and its family proteins in synapse formation and maintenance. (2010)
  • Author(s): Yuzaki, M.
  • Journal Title: Curr Opin Neurobiol Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Synapse formation and maintenance by Clq family proteins : a new class of secreted synapse organizers. (2010)
  • Author(s): Yuzaki, M.
  • Journal Title: Eur J Neurosci Volume: 32 Pages: 191-197
  • Peer Reviewed
• [Journal Article] Cbln1 is a ligand for an orphan glutamate receptor δ2, a bidirectional synapse organizer (2010)
  • Author(s): Matsuda K, Miura E, Miyzaki T, Kakegawa, W, Emi K, Narumi S, Fukazawa Y, Ito-Ishida A, Kondo T, Shigemoto R, Watanabe M, Yuzaki M
  • Journal Title: Science 328 Pages: 363-368
• [Journal Article] The N-terminal domain of GluD2 (GluR・2) recruitspresynaptic terminals and regulates synaptogenesis in the cerebellum in vivo (2009)
  • Author(s): Kakegawa W, Miyazaki T, Kohda K, Matsuda K, Emi K, Motohashi J, Watanabe M, Yuzaki M
  • Journal Title: J.Neurosci. 29 Pages: 5738-5748
• [Journal Article] Cbln1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum. (2009)
  • Author(s): Miura E, Matsuda K, Morgan J I, Yuzaki M, Watanabe M
  • Journal Title: Eur.J.Neurosci. 29 Pages: 693-706
• [Journal Article] Cbln1 binds to specific postsynaptic sites at parallel fiber-Purkinje cell synapses in the cerebellum. (2009)
  • Author(s): Matsuda K, Kondo T, Iijima T, Matsuda, S, Watanabe M, Yuzaki M
  • Journal Title: Eur.J.Neurosci. 29 Pages: 707-717
• [Journal Article] Activity-dependent repression of Cbln1 expression: mechanism for developmental and homeostatic regulation of synapses in the cerebellum. (2009)
  • Author(s): Iijima T, Emi K, Yuzaki M
  • Journal Title: J.Neurosci. 29 Pages: 5425-5434
• [Journal Article] New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the delta2 glutamate receptor. (2009)
  • Author(s): Yuzaki M
  • Journal Title: Neuroscience 162 Pages: 633-643
• [Journal Article] The N-terminal domain of GluD2 (GluRδ2) recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo (2009)
  • Author(s): Kakegawa W, Miyazaki T, Kohda K, Matsuda K, Emi K, Motohashi J, Watanabe M, Yuzaki M
  • Journal Title: J.Neurosci. 29 Pages: 5738-5748
• [Journal Article] Activity-dependent repression of Cbln1 expression: mechanism for developmental and homeostatic regulation of synapses in the cerebellum (2009)
  • Author(s): Iijima T, Emi K, Yuzaki M
  • Journal Title: J.Neurosci. 29 Pages: 5425-5434
• [Journal Article] Cbin1 accumulates and colocalizes with Cbln3 and GluRδ2 at parallel fiber-Purkinje cell synapses in the mouse cerebellum (2009)
  • Author(s): Miura, E., Matsuda, K., Morgan, J.I., Yuzaki, M., Watanabe, M.
  • Journal Title: European Journal of Neuroscience 29 Pages: 693-706
  • Peer Reviewed
• [Journal Article] Activity-dependent repression of Cbin1 expression : mechanism for developmental and homeostatic regulation of synapses in the cerebellum (2009)
  • Author(s): Iijima, T., Emi., K., Yuzaki, M.
  • Journal Title: Journal of Neuroscience 29 Pages: 5425-5434
  • Peer Reviewed
• [Journal Article] New(but old)molecules regulating synapse integrity and plasticity : Cbln1 and the δ2 glutamate receptor (2009)
  • Author(s): Yuzaki, M
  • Journal Title: Neuroscience 162 Pages: 633-643
  • Peer Reviewed
• [Journal Article] Cbln1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo. (2008)
  • Author(s): Ito-Ishida A, Miura E, Emi K, Matsuda K, Iijima T, Kondo T, Kohda K, Watanabe M, Yuzaki M
  • Journal Title: J.Neurosci. 28 Pages: 5920-5930
• [Journal Article] Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression. (2008)
  • Author(s): Nakagami R, Kohda K, Kakegawa W., Kondo T, Kato N, Yuzaki M
  • Journal Title: Keio J.Med. 57 Pages: 105-110
  • NAID: 10021988573
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluR・2. (2008)
  • Author(s): Kakegawa W, Miyazaki T, Emi K, Matsuda K, Kohda K, Motohashi J, Mishina M, Kawahara S, Watanabe M, Yuzaki M
  • Journal Title: J.Neurosci. 28 Pages: 1460-1468
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRδ2 (2008)
  • Author(s): Kakegawa W, Miyazaki T, Emi K, Matsuda K, Kohda K, Motohashi J, Mishina M, Kawahara S, Watanabe M, Yuzaki M
  • Journal Title: J.Neurosci. 28 Pages: 1460-1468
• [Journal Article] Cblnl regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo (2008)
  • Author(s): Ito-Ishida, A., Miura, E., Emi, K., Matsuda, K., Iijima, T., Kondo, T., Kohda, K. Watanabe, M., Yuzaki, M
  • Journal Title: Journal of Neuroscience 28 Pages: 5920-5930
  • Peer Reviewed
• [Journal Article] Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression (2008)
  • Author(s): Nakagami, R., Kohda, K., Kakegawa, W., Kondo, T., Kato, N., Yuzaki, M.
  • Journal Title: Keio Journal of Medicine 57 Pages: 105-110
  • NAID: 10021988573
  • Peer Reviewed
• [Journal Article] Polarized sorting of AMPA receptors to the somatodendritic domain is regulated by adaptor protein AP-4 (2008)
  • Author(s): Matsuda, S., Matsuda, K., Kakegawa, W., Miura, E., Kohda, K., Watanabe, M., Yuzaki, M.
  • Journal Title: Neuron 57 Pages: 730-745
  • NAID: 10027499929
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRδ2 (2008)
  • Author(s): Kakegawa, W., Miyazaki, T., Emi, K., Matsuda, K., Kohda, K., Motohashi, J., Mishina, M., Kawahara, S., Watanabe, M., Yuzaki, M.
  • Journal Title: Journal of Neuroscience 28 Pages: 1460-1468
  • Peer Reviewed
• [Journal Article] The ・2 "ionotropic" glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity. (2007)
  • Author(s): Kakegawa W, Kohda K, Yuzaki M
  • Journal Title: J.Physiol. 584 Pages: 89-96
• [Journal Article] Ca2+ permeability of the channel pore is not essential for the δ 2 glutamate receptor to regulate synaptic plasticity and motorcoordination. (2007)
  • Author(s): Kakegawa W, Miyazaki T, Hirai H, Motohashi J, Mishina M., Watanabe M, Yuzaki M
  • Journal Title: J.Physiol. 579 Pages: 729-735
• [Journal Article] The extreme C-terminus of GluR・2 is essential for induction of long-term depression in cerebellar slices. (2007)
  • Author(s): Kohda K, Kakegawa W, Matsuda S, Nakagami R, Kakiya N, Yuzaki M
  • Journal Title: Eur.J.Neurosci. 25 Pages: 1357-1362
• [Journal Article] Characterization of a transneuronal cytokine family Cbln-regulation of secretion by heteromeric assembly. (2007)
  • Author(s): Iijima I, Miura E, Watanabe M, Yuzaki M
  • Journal Title: Eur.J.Neurosci. 25 Pages: 1049-1057
• [Journal Article] Ho15JJ-a new hotfoot allele in a hot spot in the gene encoding the delta2 glutamate receptor. (2007)
  • Author(s): Motohashi J, Kakegawa W, Yuzaki M
  • Journal Title: Brain Res. 1140 Pages: 153-160
• [Journal Article] The delta2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity (2007)
  • Author(s): Kakegawa W, Kohda K, Yuzaki M.
  • Journal Title: Journal of Physiology 584 Pages: 89-96
  • Peer Reviewed
• [Presentation] チャネル型グルタミン酸受容体-構造生物学で解けていない問題 (2010)
  • Author(s): 柚崎通介
  • Organizer: 大阪大学蛋白質研究所セミナー「神経科学と構造生物学の融合」
  • Place of Presentation: 日大阪
  • Year and Date: 2010-10-29
• [Presentation] チャネル型グルタミン酸受容体-構造生物学で解けていない問題 (2010)
  • Author(s): 柚崎通介
  • Organizer: 大阪大学蛋白質研究所セミナー「神経科学と構造生物学の融合」
  • Place of Presentation: 大阪
  • Year and Date: 2010-10-29
• [Presentation] 分泌因子Cbln1とその受容体による小脳平行線維シナプス形成の分子機構 (2010)
  • Author(s): 松田恵子、柚崎通介
  • Organizer: 第33回日本神経科学大会シンポジウム「精神・神経活動の基盤としてのシナプス研究の最近の進歩」
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-04
• [Presentation] AMPA受容体のダイナミクスと局在化を制御する新しい機構 (2010)
  • Author(s): 柚崎通介
  • Organizer: 第33回日本神経科学大会シンポジウム「やわらかい脳を支えるイオンチャネル、受容体の局在化機構」
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] Cbln1 and its receptor : a unique and essential bidirectional synaptic organizer complex. (2010)
  • Author(s): Yuzaki, M.
  • Organizer: Keystone Symposia on Synapses : Formation, Function and Misfunction
  • Place of Presentation: Snowbird, Utah, USA
  • Year and Date: 2010-04-13
• [Presentation] Cbln1 and its receptor: a unique and essential bidirectional synaptic organizer complex. (2010)
  • Author(s): Yuzaki M
  • Organizer: Invited Talk at the Keystone Symposia on Synapses: Formation, Function and Misfunction
  • Place of Presentation: Snowbird, Utah, USA
  • Year and Date: 2010-04-13
• [Presentation] Cbln1 and its receptor: a unique and essential bidirectional synaptic organizer complex. (2010)
  • Author(s): Yuzaki M
  • Organizer: Invited Talk at the Keystone Symposia on Synapses: Formation, Function and Misfunction, Snowbird
  • Place of Presentation: Utah, USA, April 13
• [Presentation] Cbln family proteins and their receptors: unique presynaptic organizers in the cerebellum and hippocampus. (2009)
  • Author(s): Yuzaki M
  • Organizer: Selected Talk at the Gordon Conference on Excitatory Synapses and Brain Function
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 2009-09-08
• [Presentation] イオンチャネル型グルタミン酸受容体の新しい機能-孤児受容体δ2受容体から学ぶ (2009)
  • Author(s): 柚崎通介
  • Organizer: 第295回CBI学会研究講演会「神経機能・病態における細胞シグナルとイオンチャネルの制御と役割」
  • Place of Presentation: 東京
  • Year and Date: 2009-04-03
• [Presentation] Cbln family proteins and their receptors : unique presynapticorganizers in the cerebellum and hippocampus (2009)
  • Author(s): Yuzaki M.
  • Organizer: Selected Talk at the Gordon Conference on Excitatory Synapses and Brain Function
  • Place of Presentation: Les Diablerets, Switzerland, September 8
• [Presentation] Toward functional recovery of neuronal circuits-two new molecules regulating formation and maintenance of synapses in adult brain. (2008)
  • Author(s): Yuzaki M
  • Organizer: The 2nd Symposium on Brain and Mind Research in the Asia/Pacific (BMAP)
  • Place of Presentation: Singapore
  • Year and Date: 2008-09-02
• [Presentation] Toward functional recovery of neuronal circuits-two new molecules regulating formation and maintenance of synapses in adult brain (2008)
  • Author(s): Yuzaki, M.
  • Organizer: The 2nd Symposium on Brain and Mind Research in the Asia/Pacific (BMAP)
  • Place of Presentation: Singapore
  • Year and Date: 2008-09-02
• [Presentation] Cbln1ファミリータンパク質:成熟脳において急速かつダイナミックにシナプス形成と可塑性を制御する因子 (2008)
  • Author(s): 柚崎通介,飯島崇利,松田恵子,石田綾,三浦絵里子,江見恭一,幸田和久,藤哲朗,渡辺雅彦
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-25
• [Presentation] Toward functional recovery of neuronal circuits-two new molecules regulating formation and maintenance of synapses in adult brain. (2008)
  • Author(s): Yuzaki M.
  • Organizer: The 2nd Symposium on Brain and Mind Research in the Asia/Pacific (BMAP)
  • Place of Presentation: Singapore, September 2.
• [Book] トランスポートソームの世界-膜輸送研究の源流から未来へ(金井、竹島、森、久保編)(リガンド作動性チャネル) (2011)
  • Author(s): 柚崎通介
  • Publisher: 京都廣川書店
• [Book] リガンド作動性チャネルIn:トランスポートソームの世界-膜輸送研究の源流から未来へ(金井、竹島、森、久保編) (2011)
  • Author(s): 柚崎通介
  • Publisher: 京都廣川書店
• [Book] NMDA and Delta Receptors. Handbook of Neurochemistry and MolecularNeurobiology (Lajtha, A. ed)(Glutamate Receptors) (2009)
  • Author(s): Yuzaki M.
  • Publisher: Springer, New York
• [Book] Glutamate Receptors : NMDA and Delta Receptors.Handbook of Neurochemistry and Molecular Neurobiology (2009)
  • Author(s): Yuzaki M
  • Publisher: Springer
• [Book] The Glutamate Receptors. (Gereau, R.W., and Swanson, G.T. eds)(Delta receptors.) (2008)
  • Author(s): Yuzaki M.
  • Publisher: Humana Press, New Jersey
• [Book] Delta receptors.The Glutamate Receptors.(Gereau, R.W., and Swanson, G.T. eds) (2008)
  • Author(s): Yuzaki M
  • Publisher: The Humana Press
• [Book] Delta receptors. In: The Glutamate Receptors (2008)
  • Author(s): Yuzaki, M. (Gereau, R. W., Swanson, G. T. eds)
  • Total Pages: 580
  • Publisher: The Humana Press
• [Remarks] ホームページ等
  • URL: http://www.yuzaki-lab.org/
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/physiol/yuzaki/index.htm
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/physiol/yuzaki/index.htm
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/physiol/yuzaki/index.htm