Molecular mechanism of synapse differentiation and circuit formation by complex formation of secreted synapse organizer with its receptors

• Project/Area Number: 23500469
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Keio University
• Principal Investigator: MATSUDA Keiko 慶應義塾大学, 医学部, 助教 (40383765)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: シナプス形成 / シナプス可塑性 / 神経栄養因子 / シナプス / 海馬 / 神経科学 / 脳・神経 / 神経細胞 / 可塑性

Research Abstract

We had proposed a new molecular mechanism underlying cerebellar parallel fiber synapse formation; secreted Cbln1 links its two receptors, GluD2 and Neurexin, across synaptic cleft, leading bidirectional synaptic differentiation. In hippocampal CA1 pyramidal neurons, most related receptor, GluD1 is restrictedly localized in TA layer which is the most distal part in CA1 dendrites, where GluD1 is responsible for establishment of LTD. Analysis in Cbln1 or Cbln4 knockout mice, restricted localization of GluD1 in TA layer requires its ligands Cbln1 and Cbln4.
Thus we now propose the more general function of protein complex, Neurexin-Cbln-GluD in synapse formation and establishment of neuronal circuit precisely, not only in cerebellum but also in hippocampus.

Research Products

• [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: Journal of Neuroscience Volume: (in press)
  • NAID: 120005537463
  • Peer Reviewed
• [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): Konnno K., Matsuda K., Nakamoto C., Uchigashima M., Miyazaki T., Yamasaki M., Sakimura K., Yuzaki M., Watanabe M.
  • Journal Title: Journal of Neuroscience Volume: In press
  • NAID: 120005537463
  • Peer Reviewed
• [Journal Article] Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. (2012)
  • Author(s): Ito-Ishida, A., Miyazaki, T., Miura, E., Matsuda, K., Watanabe, M., Yuzaki, M and S. Okabe
  • Journal Title: Neuron Volume: 76 Pages: 549-564
  • DOI: 10.1016/j.neuron.2012.07.027
  • Peer Reviewed
• [Journal Article] Cbln1 and the Delta2 Glutamate Receptor-An Orphan Ligand and an Orphan Receptor Find Their Partners (2012)
  • Author(s): Matsuda K., Yuzaki M
  • Journal Title: Cerebellum Volume: 11 Pages: 78-84
  • DOI: 10.1007/s12311-010-0186-5
• [Journal Article] Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation (2012)
  • Author(s): Ito-Ishida A. Miyazaki T. Miura E. Matsuda K. Watanabe M. Yuzaki M. Okabe S.
  • Journal Title: Neuron Volume: 8;76(3) Pages: 549-64
  • Peer Reviewed
• [Journal Article] D-serine regulates cerebellar LTD and motor coordination through theδ2 glutamate receptor (2011)
  • Author(s): Wataru KAKEGAWA, et al
  • Journal Title: Nat Neurosci Volume: 14 Pages: 603-611
  • DOI: 10.1038/nn.2791
  • Peer Reviewed
• [Presentation] Cross talk between C1q family molecules and glutamate receptors in synapse formation (2013)
  • Author(s): Matsuda K., Yuzaki M
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] Cross talk between C1q family molecules and glutamate receptors in synapse formation
  • Author(s): Matsuda K., Yuzaki M.
  • Organizer: Neuro 2013
  • Place of Presentation: 京都
  • Invited
• [Book] Encyclopedia of Signaling Molecule (2012)
  • Author(s): Matsuda K, Yuzaki M
  • Publisher: Springer社
• [Book] Encyclopedia of Signaling Molecules, Edited by Choi S (2011)
  • Author(s): Matsuda K., Yuzaki M
  • Publisher: Springer, New York
  • URL: http://www.springer.com/biomed/human+genetics/book/978-1-4419-0460-7
• [Remarks] 慶應義塾大学医学部 生理学（柚﨑研究室）
  • URL: http://www.yuzaki-lab.org/