| Project/Area Number |
25290022
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka Yukioka College of Health Science (2016)
Nara Institute of Science and Technology (2013-2015) |
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Principal Investigator |
Shiosaka Sadao 大阪行岡医療大学, 公私立大学の部局等, 教授 (90127233)
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| Co-Investigator(Kenkyū-buntansha) |
石川 保幸 前橋工科大学, 工学部, 准教授 (90346320)
宮井 和政 秋田大学, 医学(系)研究科(研究院), 准教授 (60283933)
板東 良雄 旭川医科大学, 医学部, 准教授 (20344575)
吉田 成孝 旭川医科大学, 医学部, 教授 (20230740)
中澤 瞳 旭川医科大学, 医学部, 助教 (20712300)
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| Co-Investigator(Renkei-kenkyūsha) |
TAMURA Hideki (元)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) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | プロテアーゼ / 組織プラスミノーゲンアクティベータ / ニューロプシン / KLK8 / NRG1 / fibronectin / vitronectin / EphB2 / ニューレグリン１ / ErbB4 / 基質 / プラスミン / DPSI法 / 酵素 / 複合体 / シナプス / シグナル / 天然基質 / 神経可塑性 / 認知機能 / tPA / neuropsin |
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| Outline of Final Research Achievements |
Screening of substrates for proteases localized in the hippocampus and amygdala was carried out. Using mouse brain homogenates, we identified several candidates forming substrate-(mutant) enzyme intermediates with loop G-mutated KLK8 or tissue plasminogen activator (tPA).
NRG1 that we identified previously as a substrate of KLK8 was confirmed and further analyzed physiologically in the present study. Processing of NRG1 by KLK8 triggered ErbB4 signaling in the parvalubumin-positive inhibitory neuron and relates slow gamma oscillation of the hippocampus. Extracellular matrix proteins, fibronectin and vitronectin were also bound directly with mutant KLK8. However, we could not find direct binding of EphB2 and L1cam in the present study that were previously reported.
In addition, loop G-mutated tPA was found to bind plasminogen protein as previously reported.
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