| Project/Area Number |
22700396
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
TAMURA Hideki 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (80437516)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | Neuregulin-1 / カリクレイン / プロテオリシス / LTP / 海馬 / 神経可塑性 / 統合失調症 / 神経科学 / シナプス / 記憶・学習 / プロテアーゼ / シナプス可塑性 |
|---|
| Research Abstract |
Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect non-cleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1(NRG-1) proteolytic signaling system, which is specifically localized in microdomain of synaptic cleft. The extracellular protease, neuropsin, cleaved mature NRG-1(comprising the NRG-1 extracellular domain) at three newly-identified sites to remove the NRG-1 heparin-binding domain. This released the ligand moiety from the matrix-glycosaminoglycan pool and enabled it to phosphorylate the NRG-1 receptor, p185(ErbB4). Thus, processed-NRG-1-ErbB4 signaling contributes to the modulation of early-phase long-term potentiation of Schaffer collaterals. This signaling system may be important for both animal and human cognition, and its dysfunction may contribute to human mental disorders such as schizophrenia and bipolar disorder.
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