REGULATORY MOLECULES OF CENTRAL SYNAPSES

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249012
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: MISHINA Masayoshi 東京大学, 大学院・医学系研究科, 教授 (80144351)
• Project Period (FY): 2009 – 2011
• Keywords: グルタミン酸受容体 / 中枢シナプス / シナプス形成 / 精神疾患

Research Abstract

Elucidation of molecular mechanisms that regulate synapse formation is prerequisite for the understanding of neural wiring, higher brain functions and mental disorders. Here, we show that glutamate receptor GluRδ2 mediates cerebellar synapse formation by interacting with presynaptic neurexins through Cbln1. These results suggest that the combination of systematic proteomics and functional synapse formation assays provide efficient screening of molecules responsible for synapse formation and function, contributing to the development of brain neuropharmacology.

Research Products

• [Journal Article] Protein tyrosine phosphataseσregulates the synapse number of zebrafish olfactory sensory neurons (2011)
  • Author(s): Chen, X., Yoshida, T., Sagara, H., Mikami, Y. and Mishina, M
  • Journal Title: J. Neurochem Volume: 119 Pages: 532-543
  • DOI: DOI:10.1111/j.1471-4159.2011.07411.x
  • Peer Reviewed
• [Journal Article] IL1RAPL1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with PTPδ (2011)
  • Author(s): Yoshida, T., Yasumura, M., Uemura, T., Lee, S., Ra, M., Taguchi, R., Iwakura, Y. and Mishina, M
  • Journal Title: J. Neurosci Volume: 31 Pages: 13485-13499
  • DOI: DOI:10.1523/JNEUROSCI.2136-11.2011
  • Peer Reviewed
• [Journal Article] NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination (2011)
  • Author(s): Biase, L. D., Kang, S., Potter, E., Fukaya, F., Pucak, M., Mishina, M., Calabresi, P. and Bergles, D
  • Journal Title: J. Neurosci Volume: 31 Pages: 12650-12662
  • DOI: DOI:10.1523/JNEUROSCI.2455-11.2011
  • Peer Reviewed
• [Journal Article] Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation (2011)
  • Author(s): Kaneko, M., Yamaguchi, K., Eiraku, M., Sato, M., Takata, N., Kiyohara, Y., Mishina, M., Hirase, H., Hashikawa, T. and Kengaku, M
  • Journal Title: PLoS ONE Volume: 6 Pages: e20108
  • DOI: DOI:10.1371/journal.pone.0020108
  • Peer Reviewed
• [Journal Article] Differential interactions of cerebellin precursor protein(Cbln) subtypes and neurexin variants for synapse formation of cortical neurons (2011)
  • Author(s): Joo, J., Lee, S., Uemura, T., Yoshida, T., Yasumura, M., Watanabe, M. and Mishina, M.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 406 Pages: 627-632
  • DOI: DOI:10.1016/j.bbrc.2011.02.108
  • Peer Reviewed
• [Journal Article] Glutamate receptorδ2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells (2011)
  • Author(s): Yamasaki, M., Miyazaki, T., Azechi, H., Abe, M., Natsume, R., Hagiwara, T., Aiba, A., Mishina, M., Sakimura, K. and Watanabe, M
  • Journal Title: J. Neurosci Volume: 31 Pages: 3362-3374
  • DOI: DOI:10.1523/JNEUROSCI.5601-10.2011
  • Peer Reviewed
• [Journal Article] NR3A-containing NMDA receptors promote neurotransmitter release and spike timing-dependent plasticity (2011)
  • Author(s): Larsen, R. S., Corlew, R. J., Henson, M. A., Roberts, A. C., Mishina, M., Watanabe, M., Lipton, S. A., Nakanishi, N., Perez-Otano, I., Weinberg, R. J., and Philpot, B. D.
  • Journal Title: Nature Neurosci Volume: 14 Pages: 338-344
  • DOI: DOI:10.1038/nn.2750
  • Peer Reviewed
• [Journal Article] The physiological roles of vesicular GABA transporter during embryonic development : a study using knockout mice (2010)
  • Author(s): Hayashi, R., Nakazato, Y., Takamori, S., Ebihara, S., Uematsu, M., Mishina, M., Miyazaki, J., Yokoyama, M., Konishi, S., Inoue, K., Fukuda, A., Fukumoto, M., Nakamura, K., Obata, K., and Yanagawa, Y
  • Journal Title: Mol. Brain Volume: 3. 40
  • DOI: DOI:10.1186/1756-6606-3-40
  • Peer Reviewed
• [Journal Article] Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory (2010)
  • Author(s): Miyazaki, T., Yamasaki, M., Takeuchi, T., Sakimura, K., Mishina, M. and Watanabe, M
  • Journal Title: J. Neurosci Volume: 30 Pages: 15196-15209
  • DOI: DOI:10.1523/JNEUROSCI.0934-10.2010
  • Peer Reviewed
• [Journal Article] Essential role of NMDA receptor channelε4 subunit(GluN2D) in the effects of phencyclidine, but not methamphetamine (2010)
  • Author(s): Hagino, Y., Kasai, S., Han, W., Yamamoto, H., Nabeshima, T., Mishina, M. and Ikeda, K
  • Journal Title: PLoS ONE Volume: 5 Pages: e13722
  • DOI: DOI:10.1371/journal.pone.0013722
  • Peer Reviewed
• [Journal Article] Specific involvement of postsynaptic GluRN2B-containing NMDA receptors in the developmental elimination of corticospinal synapses (2010)
  • Author(s): Ohno, T., Maeda, H., Murabe, N., Kamiyama, T., Yoshioka, N., Mishina, M. and Sakurai, M
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 15252-15257
  • DOI: DOI:10.1073/pnas.0906551107
  • Peer Reviewed
• [Journal Article] Trans-synaptic interaction of GluRδ2 and neurexin through Cbln1 mediates synapse formation in the cerebellum (2010)
  • Author(s): Uemura, T., Lee, S., Yasumura, M., Takeuchi, T., Yoshida, T., Ra, M., Taguchi, R., Sakimura, K. and Mishina, M.
  • Journal Title: Cell Volume: 141 Pages: 1068-1079
  • DOI: DOI:10.1016/j.cell.2010.04.035
  • Peer Reviewed
• [Journal Article] Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability (2010)
  • Author(s): Mozhui, K., Karlsson, R-M., Kash, T. L., Ihne, J., Norcross, M., Patel, S., Farrell, M. R., Hill, E., Martin, K., Camp, M., Fitzgerald, P. J., Ciobanu, D. C., Sprengel, R., Mishina, M., Wellman, C. L., Winder, D. G., Williams, R. W., and Holmes, A
  • Journal Title: J. Neurosci Volume: 30 Pages: 5357-5367
  • DOI: DOI:10.1523/JNEUROSCI.5017-09.2010
  • Peer Reviewed
• [Journal Article] Estrogen regulates the expression of N-methyl-D-aspartate(NMDA) receptor subunit epsilon 4(Grin2d), that is essential for the normal sexual behavior in female mice (2010)
  • Author(s): Ikeda, K., Fukushima, T., Ogura, H., Tsukui, T., Mishina, M., Muramatsu, M. and Inoue, S
  • Journal Title: FEBS Lett Volume: 584 Pages: 806-810
  • DOI: DOI:10.1016/j.febslet.2009.12.054
  • Peer Reviewed
• [Journal Article] Regulation of synaptic vesicle accumulation and axon terminal remodeling during synapse formation by distinct Ca^<2+> signaling (2009)
  • Author(s): Yoshida, T., Uchida, S. and Mishina, M
  • Journal Title: J. Neurochem Volume: 111 Pages: 160-170
  • DOI: DOI:10.1111/j.1471-4159.2009.06309.x
  • Peer Reviewed
• [Journal Article] NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss (2009)
  • Author(s): Longordo, F., Kopp, C., Mishina, M., Lujan, R. and Luthi, A
  • Journal Title: J. Neurosci Volume: 29 Pages: 9026-9041
  • DOI: DOI:10.1523/JNEUROSCI.1215-09.2009
  • Peer Reviewed
• [Presentation] Identification of a novel ligand for glutamate receptorδ2(July 22) (2010)
  • Author(s): Mishina, M., Uemura, T., Lee, S., Yasumura, M. and Yoshida, T
  • Organizer: The 16^<th> World Congress on Basic and Clinical Pharmacology
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 20100717-23
• [Presentation] Glutamate receptor signaling in learning and neural wiring (2010)
  • Author(s): Mishina, M
  • Organizer: Korean Society for Biochemistry and Molecular Biology(KSBMB) Annual Meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20100517-19
• [Remarks] 新聞報道(1)科学新聞「小脳のグルタミン酸受容体シナプス形成導く精神疾患解明期待東大・三品教授ら成果」2010年6月11日
• [Remarks] (2)朝日新聞「脳機能障害克服へ一歩」2010年6月4日
• [Remarks] (3)日本経済新聞「つなぎ目構造解明東大、自閉症薬などに道」2010年5月28日
• [Remarks] (4)日刊工業新聞「東大、分子機構を解明シナプス結合の形成」2010年5月28日