| Project/Area Number |
11680772
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
YAMAGATA Kanato Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 副参事研究員 (20263262)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Hiroko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 研究員 (40162870)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Neural activity / cell adhesion molecule / arcadlin / MAPキナーゼ / シナプス / 神経可塑性 |
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| Research Abstract |
To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are repidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent synaptic activity in LTP.The extracellular domain of Arcadlin is most homologous to protocadherin-8 ; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses and shows a homophilic binding activity in a Ca^<2+>-dependent manner. Application of Arcadlin antibody reduces EPSP amplitude and blocks LTP in hippocampal slices. Two-hybrid screening identified the cytoplasmic region bound to TAO2 kinase. Furthermore, homophilic binding of extracellular domains activated the cytoplasmic region of Arcadlin, TAO2, MKK3 and p38 MAP kinase sequentially. Its close homology with cadherins, its rapid inducibility by neural activity, its involvement in synaptic transmission and its activation of p38 MAP kinase pathway suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory.
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