2011 Fiscal Year Final Research Report
Molecular mechanism of effect of secreted active neuropsin on neighboring synapses
| 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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| 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 |
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| 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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Research Products
(13 results)
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[Journal Article] Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin2010
Author(s)
Shingaki K, Matsuzaki S, Taniguchi M, Kubo T, Fujiwara T, Kanazawa S, Yamamoto A, Tamura H, Maeda T, Ooi K, Matsumoto K, Shiosaka S and Tohyama M
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Journal Title
Br J Dermatol.
Volume: 163
Pages: 466-475
Peer Reviewed
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[Presentation] Potential fluorescent imaging for on-chip cultured neurons, acute slice, and visual cortex by using an implantable imaging device2011
Author(s)
Kobayashi T, Tamura H, Hatanaka Y, Motoyama M, Noda T, Sasagawa K, Tokuda T, Ishikawa Y, Shiosaka S and Ohta J
Organizer
Society for Neuroscience 2011
Place of Presentation
Washington DC, USA
Year and Date
2011-11-13
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