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Pharmacological studies of calmodulin-dependent tau factor phosphorylation in cultured cerebellar granule cells.

Research Project

Project/Area Number 02671056
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionKumamoto Research (C)

Principal Investigator

FUKUNAGA Kohji  Kumamoto Univ. Med. Sch. Assistant Professor, 医学部, 講師 (90136721)

Co-Investigator(Kenkyū-buntansha) YAMAKAWA Takashi  Kumamoto Univ. Med. Sch. Research Associate, 医学部, 助手 (10230327)
MIYAMOTO Eishichi  Kumamoto Univ. Medi. Sch. Professor, 医学部, 教授 (50109659)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsCa^<2+> / Calmodulin / Protein kinase / Cerebellar granule cells / Hippocampal neurons / NMDA receptor / Glutamate / Long-term potentiation / カルシウムイオン / 培養神経細胞 / グルタミン酸受容体 / 脳の可塑性 / 微小管蛋白質
Research Abstract

Ca^<2+>/calmodulin-dependent protein kinase II(CaM kinase II), which is highly enriched in neural tissues, is a multifunctional protein kinase that is involved in regulation of biosynthesis and release of neurotransmitter, and expression of long-term potentiation(LTP)in CAl region of the hippocampus. Recently, it has been shown in vitro that autophosphorylation of Thr-286/287(alpha/beta subunits)in the CaM kinase II converts it from the Ca^<2+>-dependent form to a partially Ca^<2+>-independent species. We reported evidence for the formation of Ca^<2+>-independent CaM kinase II in cerebellar granule cells following the activation of the glutamate-induced NMDA receptor. In the granule cells, there was a good temporal correlation between autophosphorylation of Thr-287 in CaM kinase II and generation of Ca^<2+>-independent kinase activity. However, as brief exposure(30 sec)of granule cells to glutamate resulted in a relatively transient(<5 min)increase in the Ca^<2+>-independent activity o … More f CaM kinase II. Therefore, we have focused attention on the hippocampal tissue, since involvement of NMDA receptor in the LTP has been clearly shown in the tissue. In cultured hippocampal neurons, glutamate did elevated the Ca^<2+>-independent activity of CaM kinase II as in cerebellar granule cells. The maximal effect on the Ca^<2+>-independence was greater than that in the granule cells and the activity was more stable for at least 30 min in the continued presence of glutamate. In the experiments with _<32>P-labeled cells, the phosphorylation of MAP2 as well as autophosphorylation of CaM kinase II were found to be stimulated by the exposure to glutamate. These results were consistent with the hypothesis that the increase in the postsynaptic Ca^<2+> influx through the NMDA receptor-gated ion channel converts CaM kinase II to a constitutively active, Ca^<2+>-independent form in the hippocampal neurons, and results in an increase in the phosphorylation of target proteins such as MAP2 for the enzyme. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Koji Fukunaga: "Activation of Ca^<2+>/calmodulin-dependent protein kinase II in cerebellar granule cells by N-methyl-D-aspartate receptor activation" Molecular and Cellular Neurosciences. 1. 133-138 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hideyuki Yamamoto: "Dephosphorylation of τ factor by protein phosphatase 2A in Synaptosomal cytosol fractions,and inhibition by aluminum" Journal of Neurochemistry. 55. 683-690 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Setsuko Yasugawa: "Autophosphorylation of Ca^<2+>/calmodulin-dependent protein kinase II:Effects on interaction between enzyme and substrate" Japanese Journal of Pharmacology. 55. 263-274 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takashi Ohba: "Possible involvement of the Ca^<2+>/calmodulin-dependent signal transduction system in rat granulosa cells" Biomedical Research. 12. 25-33 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 宮本 英七: "細胞系におけるCa^<2+>/カルモデュリン依存性プロテインキナ-ゼIIの細胞刺激に反応した調節" 日本薬理学雑誌. 98. 177-185 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Motohiro Morioka: "Regional and temporal alterations in Ca^<2+>/calmodulin-dependent protein kinase II and calcineurin in the hippocampus of rat brain after transient forebrain ischemia" Journal of Neurochemistry. 58. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Thomas R.Soderling: "Progressi in Brain Rersearch,Vol.89,pp.169-183,"Molecular and cellular studies on brain calcium/calmodulin-dependent protein kinase II"" Elsevier,Amsterdam, 446 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kohji Fukunaga: "Excitatory Amino Acids,pp.159-165,"Excitatory amino acids and protein kinases"" Thimeme Medical Publishers,Inc.,New York, 292 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koju Fukunaga: "Activation of Ca^<2+>/calmodulinーdependent protein kinase II in cerebellar granule cells by NーmethylーDーaspatrate receptor activation" Molecular and Cellular Neurosciences. 1. 133-138 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hideyuki Yamamoto: "Dephosphorylation of τ factor by protein phosphatase 2A in synaptosomal cytosol fractions,and inhibition by aluminum" Journal of Neruochemistry. 55. 683-690 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Setsuko Yasugawa: "Autophosphorylation of Ca^<2+>/calmodulinーdependent protein kinase II:Effects on interaction between enzyme and substrate" Japanese Journal of Pharmacology. 55. 263-274 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Thomas R.Soderling: "Molecular and cellular studies on brain calcium/calmodulinーdependent protein kinase II" Progress in Brain Research. 89. 169-183 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 宮本 英七: "細胞系におけるCa^<2+>/カルモデュリン依存性プロテインキナ-ゼIIの細胞刺激に反応した調節" 日本薬理学雑誌. 98. 177-185 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Motohiro Morioka: "Regional and temporal alterations in Ca^<2+>/calmodulinーdependent protein kinase II and calcineurin in the hippocampus of rat brain after transient forebrain ischemia" Journal of Neurochemistry. 58. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Koji Fukunaga: "Activation of Ca^<2+>/calmodulinーdependent protein kinase II in cerebellar granule cells by NーmethylーDーaspartate receptor activation" Molecular and Cellular Neurosciences. 1. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hideyuki Yamamoto: "Dephosphorylation of τ factor by protein phosphatase 2A in synaptosomal cytosol fractions,and inhibition by aluminum" Journal of Neurochemistry. 55. 683-690 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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