Establishment of Proteogenomics

• Project/Area Number: 19209007
• 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 The University of Tokyo, 大学院・医学系研究科, 教授 (80144351)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Tomoyuki 東京大学, 大学院・医学系研究科, 助教 (90372367)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000); Fiscal Year 2008: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2007: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
• Keywords: 軸索終末分化 / シナプス小胞 / 形態変化 / 可視化 / 精神遅滞 / プロテオミクス / ゼブラフィッシュ / 嗅神経細胞 / シナプス形成 / カルシウムシグナル / カルモジュリン / イノシトール3リン酸 / 電位依存性カルシウムチャンネル

Research Abstract

本研究では、神経細胞がシナプスを形成する過程をin vivo で可視化し観察出来るゼブラフィッシュを用いて、精神遅滞の原因遺伝子の一つであるIL1RAPL1 が嗅神経細胞軸索の終末におけるシナプス小胞の集積と形態変化を制御していることを明らかにした.さらに、IL1RAPL1 と結合する蛋白質をプロテオミクス解析で同定した.ゼブラフィッシュ機能解析系との組み合わせによるプロテオゲノミックス分野の開拓は、創薬の標的となる機能分子を提示することにより脳の機能障害や脳の発達障害などの克服に貢献するものと思われる.

Research Products

• [Journal Article] M. Influence of parallel fiber-purkinjecell synapse formation on postnataldevelopment of climbing fiber-Purkinjecell synapses in the cerebellum (2009)
  • Author(s): Hashimoto, K., Yoshida, T., Sakimura, K., Mishina, M., Watanabe, M., and Kano
  • Journal Title: Neuroscience(in press)
  • Peer Reviewed
• [Journal Article] Influence of parallel fiber-purkinje cell synapse formation on postnatal development of climbing fiber-purkinje cell synapses in the cerebellum. (2009)
  • Author(s): Hashimoto, K. , Yoshida, T. , Sakimura, M. , Mishina, M. , Watanabe, M. , and Kano, M.
  • Journal Title: Neuroscience (in press)(印刷中(掲載確定))
  • Peer Reviewed
• [Journal Article] Theamino-terminal domain of glutamatereceptor 2 triggers presynapticdifferentiation. Biochem. Biophys. Res (2008)
  • Author(s): Uemura, T. and Mishina, M
  • Journal Title: Commun 377 Pages: 1315-1319
  • Peer Reviewed
• [Journal Article] Zebrafishorthologue of mental retardationprotein IL1RAPL1 regulates presynapticdifferentiation (2008)
  • Author(s): Yoshida, T. and Mishina, M
  • Journal Title: Mol. Cell. Neurosci. 39 Pages: 218-228
  • Peer Reviewed
• [Journal Article] Role of the internal Shank-bindingsegment of glutamate receptor δ2 insynaptic localization and cerebellarfunctions (2008)
  • Author(s): Yasumura, M., Uemura, T., Yamasaki, M., Sakimura, K., Watanabe, and M. Mishinan, M
  • Journal Title: Neurosci. Lett. 433 Pages: 146-151
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation oncerebellar foliation, Bergmann gliapositioning and climbing fiberterritory on Purkinje cells (2008)
  • Author(s): Watanabe, F., Miyazaki, T., Takeuchi,T., Fukaya, M., Nomura, T., Noguchi, S., Mori, H., Sakimura, K., Watanabe, M. and Mishina, M
  • Journal Title: Eur. J.Neurosci 27 Pages: 836-854
  • Peer Reviewed
• [Journal Article] Zebrafish orthologue of mental retardation protein IL1RAPL1 regulates presynaptic differentiation. (2008)
  • Author(s): Yoshida, T. and Mishina, M.
  • Journal Title: Mol. Cell. Neurosci. 39 Pages: 218-228
  • Peer Reviewed
• [Journal Article] The amino-terminal domain of glutamate receptor σ82 triggers Presynaptic differentiation. (2008)
  • Author(s): Uemura, T. , and Mishina, M.
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 1315-1319
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiberterritory on Purkinje cells (2008)
  • Author(s): Watanabe, F., et. al.
  • Journal Title: Eur.J.Neurosci 27 Pages: 836-854
  • Peer Reviewed
• [Journal Article] Role of the internal Shank-binding segment of glutamate receptor δ2 in synaptic localization and cerebellar functions (2008)
  • Author(s): Yasumura, M., et. al.
  • Journal Title: Neurosci.Lett 433 Pages: 146-151
  • Peer Reviewed
• [Journal Article] Identification andcharacterization of zebrafishsemaphoring 6D (2007)
  • Author(s): Kimura, M., Taniguchi, M., Mikami, Y.,Masuda, T., Yoshida, T., Mishina, M. and Shimizu, T
  • Journal Title: Biochem. Biophys. Res.Commun 363 Pages: 762-768
  • Peer Reviewed
• [Journal Article] Regulation of long-termdepression and climbing fiber territoryby glutamate receptor δ2 at parallelfiber synapses through its C-terminaldomain in cerebellar Purkinje cells (2007)
  • Author(s): Uemura, T., Kakizawa, S., Yamasaki, M.,Sakimura, K., Watanabe, M., Iino, M. and Mishina, M
  • Journal Title: J.Neurosci 27 Pages: 12096-12108
  • Peer Reviewed
• [Journal Article] Activation ofNMDA receptors promotes dendritic spinedevelopment through MMP-mediated ICAM-5cleavage (2007)
  • Author(s): Tian, L., Stefanidakis, M., Ning, L.,Lint, P. V., Nyman-Huttunen, H., Libert, C., Itohara, S., Mishina, M. and Rauvala, H. Gahmberg, C. G
  • Journal Title: J. Cell Biol 178 Pages: 687-700
  • Peer Reviewed
• [Journal Article] Regulation of dendritogenesis via alipid (2007)
  • Author(s): Takemoto-Kimura, S., Ishihara-Ageta, N., Nonaka, M., Adachi-Morishima, A.,Mano, T., Okamura, M., Fujii, H., Fuse, T., Hoshino, M., Suzuki, S., Kojima, M., Mishina, M., Okuno, H. and Bito, H
  • Journal Title: raft-associatedCa2+/calmodulin-dependent proteinkinase CLICK-III/CaMKI 54 Pages: 755-770
  • Peer Reviewed
• [Journal Article] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent proteinkinase CLICK-III/CaMKly (2007)
  • Author(s): Takemoto-Kimura, S., et. al.
  • Journal Title: Neuron 54 Pages: 755-770
  • Peer Reviewed
• [Journal Article] Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage (2007)
  • Author(s): Tian, L., et. al.
  • Journal Title: J.Cell Biol 178 Pages: 687-700
  • Peer Reviewed
• [Journal Article] Regulation of long-term depression and climbing fiber territory by glutamate receptor δ2 at parallelfiber synapses through its C-terminal domain in cerebellar Purkinje cells (2007)
  • Author(s): Uemura, T., et. al.
  • Journal Title: J.Neurosci 27 Pages: 12096-12108
  • Peer Reviewed
• [Journal Article] Identification and characterization of zebrafish semaphoring6D (2007)
  • Author(s): Kimura, M., et. al.
  • Journal Title: Biochem.Biophys.Res.Commun 363 Pages: 762-768
  • Peer Reviewed
• [Presentation] The ectopic location of Bergmann gliaand altered climbing fiber territory onPurkinje cells by FAK ablation (2008)
  • Author(s): F. Watanabe, T. Miyazaki, T. Takeuchi, K. Sakimura, M. Watanabe and M. Mishina
  • Organizer: The 31thAnnual Meeting of the Japan neuroscience Society
  • Place of Presentation: TokyoInternational Forum, Japan
  • Year and Date: 2008-10-07
• [Presentation] Role of the C-terminal PDZbinding domain of glutamate receptor 2in synaptic plasticity and climbingfiber wiring (2008)
  • Author(s): T. Uemura, S. Kakizawa, M. Yamasaki, K.Sakimura, M. Watanabe, M. Iino and M.Mishina
  • Organizer: The 31th Annual Meeting ofthe Japan neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-11
• [Presentation] Role of the internal Shank-binding segment of GluRδ2 in cerebellar functions (2008)
  • Author(s): M. Yasumura, T. Uemura, M. Yamasaki, K.Sakimura, M. Watanabe and M. Mishina
  • Organizer: The 31th Annual Meeting ofthe Japan neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-11
• [Presentation] Role of the C-terminal PDZ binding domain of glutamate receptor σ2 in synaptic plasticity and climbing fiber wiring. (2008)
  • Author(s): T. Uemura, S. Kakizawa, M. Yamasaki, K. Sakimura, M. Watanabe, M. Iino and M. Mishina
  • Organizer: The 31^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-11
• [Presentation] Role of the internal Shank-binding segment of GluRσ2 in cerebellar functions. (2008)
  • Author(s): M. Yasumura, T. Uemura, M. Yamasaki, K. Sakimura, M. Watanabe and M. Mishina
  • Organizer: The 31^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-11
• [Presentation] Zebrafishorthologue of mental retardationprotein IL1RAPL1 regulates axonterminal differentiation (2008)
  • Author(s): T. Yoshida and M. Mishina
  • Organizer: The 31thAnnual Meeting of the Japan neuroscienceSociety
  • Place of Presentation: TokyoInternational Forum, Japan
  • Year and Date: 2008-07-10
• [Presentation] The ectopic location of Bergmann glia and altered climbing fiber territory on Purkinje cells by FAK ablation. (2008)
  • Author(s): F. Watanabe, T. Miyazaki, T. Takeuchi, K. Sakimura, M. Watanabe and M. Mishina
  • Organizer: The 31^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-10
• [Presentation] Zebrafish orthologue of mental retardation protein IL1RAPL1 regulates axon terminal differentiation. (2008)
  • Author(s): T. Yoshida and M. Mishina
  • Organizer: The 31^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Tokyo International Forum, Japan
  • Year and Date: 2008-07-10
• [Presentation] Distinct calcium signaling forsynaptic vesicle accumulation andmorphological remodeling during axonterminal differentiation of zebrafisholfactory sensory neurons (2008)
  • Author(s): T. Yoshida, A. Uotsu, S. Uchida and M. Mishina
  • Organizer: The 81stAnnual Meeting of the JapanesePharmacological Society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2008-03-19
• [Presentation] Distinct caicium signaling for synaptic veside accumulation and morphological remodeling duringaxon terminal differentiation of zebrafish olfactory sensory neurons (2008)
  • Author(s): Yoshida, T., et. al.
  • Organizer: The 81st Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2008-03-19
• [Presentation] Roles of the internal PDZ-binding domainof GluR2 in synaptic localization andcerebellar functions (2008)
  • Author(s): M. Yasumura, T. Uemura, M. Yamasaki, K.Sakimura, M. Watanabe and M. Mishina
  • Organizer: The 81st AnnualMeeting of the Japanese PharmacologicalSociety
  • Place of Presentation: Pacifico Yokohama, Japan
  • Year and Date: 2008-03-17
• [Presentation] Roles of the internal PDZ-binding domain of GluRδ2 in synaptic localization and cerebellar functions (2008)
  • Author(s): Yasumura, M., et. al.
  • Organizer: The 81st Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2008-03-17
• [Presentation] Receptor proteintyrosine phosphatase s regulatessynaptic vesicle accumulation in axonterminals of zebrafish olfactorysensory neurons (2007)
  • Author(s): X. Chen, T. Yoshida, Y. Mikami, H.Sagara and M. Mishina
  • Organizer: Society forNeuroscience 37th Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-06
• [Presentation] Receptor protein tyrosine phosphatase S regulates synaptic vesicle accumulation in axon terminals of zebrafish olfactory sensory neurons (2007)
  • Author(s): Chen, X., et. al.
  • Organizer: Society for Neuroscience 37th Annual Meeting
  • Place of Presentation: San Diego,USA
  • Year and Date: 2007-11-06
• [Presentation] Identification of a novel zebrafish semaphorin (2007)
  • Author(s): Taniguchi, M., et. al.
  • Organizer: The 30th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2007-09-11
• [Presentation] Identification of a novelzebrafish semaphorin (2007)
  • Author(s): M. Taniguchi, Y. Mikami, T. Masuda, M.Kimura, T. Yoshida, M. Mishina and T.Shimizu
  • Organizer: The 30th AnnualMeeting of the Japan neuroscienceSociety
  • Place of Presentation: Pacifico Yokohama, Japan