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Studies on the Roles of Ras femily GTPases in the Signal Transduction in Hyppocampal Neuronal Cells.

Research Project

Project/Area Number 13680860
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo (2002)
National Center of Neurology and Psychiatry (2001)

Principal Investigator

HATTORI Seisuke  Institute of Medical Sciences, Visiting Professor, 医科学研究所, 客員教授 (50143508)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsRas / Gap1m / Hippocampus / Glutamate Receptors / MAP kinase / Rin / 海馬神経細胞 / Rap1 / アデノウイルスベクター / GTPase-activating protein
Research Abstract

Mitogen-activated protein (MAP) kinase plays important roles in the establishment of long term potentiation both in vitro and in living animals. MAP kinase is activated in response to a broad range of stimuli including calcium influx through N-methyl-D-aspartate (NMDA) receptor and L-type calcium channel, cAMP, and neurotrophins. To investigate the role of Ras in the activation of MAP kinase and CREB (cAMP response element-binding protein) in hippocampal neurons, we inhibited Ras function by overexpressing a Ras GTPase- activating protein, Gap1m, or dominant negative Ras by means of adenovirus vectors. Gap1m expression almost completely suppressed MAP kinase activation in response to NMDA, calcium ionophore, membrane depolarization, forskolin, and brain-derived neurotrophic factor (BDNF). Dominant negative Ras also showed the similar effects. On the other hand, Rap1 GAP did not significantly inhibit the forskolin-induced activation of MAP kinase. These results demonstrate that Ras transduces signals elicited by a broad range of stimuli to MAP kinase in hippocampal neurons.
We also analyzed Rap1 function in cultured cells. Upon introduction of factors that activated Rap1, enhancement of cell adhesion property was observed. Dominant negative Rap1 blocked this enhancement and dominat active Rap1 strongly activated the cell adhesion, suggenting the role of Rap1 in cell adhesion.
Moreover, we made a gene targeting mouse for Rin, a Ras-like GTPase expressed secifically only in neuronal tissues. This Rin knockout mouse maybe very useful for the functional study of Rin in vivo.

Report

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

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Sakakibara A, Ohba Y, Kurokawa K, Matsuda M, Hattori S: "Novel function of Chat in controlling cell adhesion via Cas-Crk C3G-pathway-mediated Rap1 activation"Journal of Cell Science. 115. 4915-4924 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iida N, Namikawa K, Kiyama H, Ueno H, Nakamura S, Hattori S: "Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons"Journal of Neuroscience. 21. 6459-6466 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakakibara A, Ohba Y, Kurokawa K, Matsuda M, Hattori S: "Novel function of Chat in controlling eel adhesion via Cas-Crk-C3G-pathway-mediated Rap1activation"Journal of Cell Science. 115. 4915-4924 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iida N. Namikawa. K, Kiyama. H, Ueno. H, Nakamura. S, Hattori. S: "Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons"Journal of Neuroscience. 21. 6459-6466 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakakibara A, Hattori S, Nakamura S, Katagiri T: "A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells"J.Biol.Chem.. 278. 6012-6017 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakakibara A, Ohba Y, Kurokawa K, Matsuda M, Hattori S: "Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation"J.Cell Sci.. 115. 4915-4924 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iida, N., Namikawa, K., Kiyarna, H., Ueno H., Nakamura, S., Hattori S.: "Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons"J. Neurosci. 21・17. 6459-6466 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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