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Analysis of Molecular Assembly of Synaptic Molecules during Development

Research Project

Project/Area Number 12470001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OKABE Shigeo  Tokyo Medical and Dental Univ., Dept of Cell Biology, Professor, 大学院・医歯学総合研究科, 教授 (60204012)

Co-Investigator(Kenkyū-buntansha) INOUE Akihiro  Tokyo Medical and Dental Univ., Dept of Cell Biology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80322080)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordssynapse / hippocampus / fluorescence microscopy / postsynaptic density / dendritic spine / green fluorescent protein(GFP) / intracellular calcium
Research Abstract

Transition of excitatory synapses from dendritic shafts to spines takes place during the period of 10-20 days in culture of hippocampal pyramidal neurons. This culture system provides a good model for the study of formation and remodeling of synaptic structure. To analyze dynamic properties of multiple postsynaptic density (PSD) proteins, we generated green fluorescent protein (GFP)-tagged PSD proteins, such as PSD-95 and PSD-Zip45 (also known as Homer Ic), together with presynaptic marker synaptophysin. The first set of experiments aimed at revealing time-course of morphogenesis of dendritic spines, assembly of PSD proteins, and accumulation of synaptic vesicles at single synaptic junctions. We performed dual-wavelength, time-lapse fluorescence microscopy of living hippocampal neurons and revealed temporal correlation among these three events. Furthermore, synaptogenesis was a rapid process, which took place less than an hour. In the second research project we analyzed dynamic redistr … More ibution of PSD-Zip45 after stimulation of cultured neurons. In contrast to the stable nature of PSD-95 after stimulation, PSD-Zip45 changed its distribution bidirectionally after increase of the intracellular calcium. This result indicates the presence of molecular mechanism that drives PSD-Zip45-specific translocation by the neuronal activity. In the third set of experiments we generated transgenic mice expressing either GFP-tagged PSD-95 or PSD-Zip45 to achieve stable expression of probe molecules in the hippocampus. Using cultured neurons isolated from the transgenic hippocampus, we characterized slow remodeling of PSD-95 and PSD-Zip45 clusters for >1 week. The results indicate the presence of cAMP-dependent signaling system that regulates the average density of PSD clusters within a single cell. In summary, these three sets of experiments revealed novel molecular dynamics of PSD proteins in living neurons and regulation of the distribution of PSD proteins by complex signaling system that can be differentially activated by various neuronal activities. Less

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Kondo, M., Okabe, S., Sumino, R., H.Okado: "High GluR1/GluR2 expression ratio correlates with expression of Ca2+-binding proteins in the rat forebrain neurons"Europoean Journal of Neuroscience. 12. 2812-2822 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Umeda, T., S.Okabe: "Visualizing synapse formation and remodeling : recent advances in real-time imaging of CNS synapses"Neuroscience Research. 40. 291-300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Miwa, A., H.Okado: "Spine formation and correlated assembly of presynaptic and postsynaptic molecules"Journal of Neuroscience. 21. 6105-6114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Urushido, T., Konno, D., Okado, H., K.Sobue: "Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels"Journal of Neuroscience. 21. 9561-9571 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara, T., Komiya, Y., Izumi-Nakaseko, H., Adachi-Akahane, S., Okabe, S., Okamura, Y.: "Coexpression of a Cav1.2 protein lacking N-terminus and the first domain specifically suppresses L-type calcium channel activity"FEBS Letters. 529. 203-207 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Birth, growth, and elimination of a single synapse"Anatomical Science International. 77. 203-210 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S., Hatano, O., Kawahara, N., Tamura.A., Kirino, T., M.Nakafuku: "Regeneration of hippocampal pyramidal neurons by recruitment of endogenous neural progenitors : An animal model for a neuronal replacement therapy for ischemic brain injury"Cell. 110. 429-441 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara, T., Kawabata, I., Usui, S., Sobue, K., S.Okabe: "Synchronized formation and remodeling of postsynaptic densities : long-term visualization of hippocampal neurons expressing postsynaptic density proteins tagged with GFP"Journal of Neuroscience. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui, S., Konno, D., Hori, K., Maruoka, H., Okabe.S., Fujikado, T., Tano, Y., K.Sobue: "Synaptic targeting of PSD-Zip45 (Homer 1C) and its involvement in the synaptic accumulation of F-actin"Journal of Biological Chemistry. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto, M., Shinomiya, K., S.Okabe: "Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord"European Journal of Neuroscience. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa, T., Watabe, A.M., Tezuka, T., Yoshida, Y., Yokoyama, K., Umemori, H., Inoue, A., Okabe.S., Manabe, T., T.Yamamoto: "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPase, is involved in the NMDA receptor signaling"Molecular and Cellular Biology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue A., S.Okabe: "The dynamic organization of postsynaptic proteins : translocating molecules regulate synaptic function"Current Opinion in Neurobiology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kondo, M., Okabe, S., Sumino, R., and H, Okado.: "High GluR1/GluR2 expression ratio correlates with expression of Ca^2+-binding proteins in the rat forebrain neurons"Europoean Journal of Neuroscience. 12. 2812-2822 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Umeda, T. and S. Okabe.: "Visualizing synapse formation and remodeling : recent advances in real-time imaging of CNS synapses"Neuroscience Research. 40. 291-300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Miwa, A., and H. Okado.: "Spine formation and correlated assembly of presynaptic and postsynaptic molecules"Journal of Neuroscience. 21. 6105-6114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S., Urushido, T., Konno, D., Okado, H., and K. Sobue.: "Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels"Journal of Neuroscience. 21. 9561-9571 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara, T., Komiya, Y., Izumi-Nakaseko, H., Adachi-Akahane, S., Okabe, S., and Okamura, Y.: "Coexpression of a Ca_v1.2 protein lacking N-terminus and the first domain specifically suppresses L-type calcium channel activity"FEBS Letters. 529. 203-207 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe, S.: "Birth, growth, and elimination of a single s ynapse"Anatomical Science International. 77. 203-210 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S., Hatano, O., Kawahara, N., Tamura, A., Kirino, T. and M. Nakafuku.: "Regeneration of hippocampal pyramidal neurons by recruitment of endogenous neural progenitors ; An animal model for a neuronal replacement therapy for ischemic brain injury"Cell. 110. 429-441 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ebihara, T., Kawabata, I., Usui, S., Sobue, K., and S. Okabe.: "Synchronized formation and remodeling of postsynaptic densities : long-term visualization of hippocampal neurons expressing postsynaptic density proteins tagged with GFP"Journal of Neuroscience. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Usui, S., Konno, D., Hori, K, Maruoka, H., Okabe, S., Fujikado, T., Tano, Y., and K. Sobue.: "Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin"Journal of Biological Chemistry. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto, M., Shinomiya, K., and S. Okabe: "Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord"European Journal of Neuroscience. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa, T., Watabe, A. M., Tezuka, T., Yoshida, Y., Yokoyama, K., Umemori, H., Inoue, A., Okabe, S., Manabe, T., and T. Yamamoto.: "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPase, is involved in the NMDA receptor signaling"Molecular and Cellular Biology. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue, A., and S. Okabe.: "The dynamic organization of postsynaptic proteins : translocating molecules regulate synaptic function"Current Opinion in Neurobiology. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S., Hatano, 0., Kawahara, N., Tamura, A., Kirino, T., M.Nakafuku: "Regeneration of hippocampal pyramidal neurons by recruitment of endogenous neural progenitors : An animal model for a neuronal replacement therapy for ischemic brain injury"Cell. 110. 429-441 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okabe, S.: "Birth, growth, and elimination of a single synapse"Anatomical Science International. 77. 203-210 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ebihara, T., Komlya, Y., Izumi-Nakaseko, H., Adachi-Akahane, S., Okabe, S., Okamura, Y.: "Coexpression of a Cav1.2 protein lacking N-terminus and the first domain specifically suppresses L-type calcium channel activity"FEBS Letters. 529. 203-207 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Usui, S., Konno, D., Hori, K., Maruoka, H., Okabe, S., K.Sobue.: "Synaptic targeting of PSD-Zip45 (Homer 1 c) and its involvement in the synaptic accumulation of F-actin"Journal of Biological Chemistry. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto, M., Shinomiya, K., S.Okabe: "Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord"Europian journal of Neuroscience. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ebihara, T., Kawabata, I., Usui, S., Sobue, K., S.Okabe: "Synchronized formation and remodeling of postsynaptic densities: long-term visualization of hippocampal neurons expressing postsynaptic density proteins tagged with GF"Journal of Neuroscience. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue, A., S.Okabe: "The dynamic organization of postsynaptic proteins : translocating molecules regulate synaptic function"Current Opinion in Neurobiology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Okabe, S., Urushido, T., Konno, D., Okado, H., K.Sobue: "Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels"Journal of Neuroscience. 21・2. 9561-9571 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okabe, S, Miwa, A., H. Okado: "Spine formation and correlated assembly of presynaptic and postsynaptic molecules"Journal of Neuroscience. 21・2. 6105-6114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Umeda, T., S.Okabe: "Visualizing synapse formation and remodeling : recent advances in real-time imaging of CNS synapses"Neuroscience Research. 40. 291-300 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kondo,M.,Okabe,S.,Sumino,R.,and H.Okado: "High GluR1/GluR2 expression ratio correlates with expression of Ca2+-binding proteins in the rat forebrain neurons."Europoean Journal of Neuroscience. 12・8. 2812-2822 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岡部繁男: "シナプス後肥厚部の機能分子-NMDA受容体とその結合蛋白質PSD-95を中心として-"解剖学雑誌. 76・2(発表予定). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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