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Screening of plasticity-relating protease substrates and their signaling system

Research Project

Project/Area Number 25290022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka Yukioka College of Health Science (2016)
Nara Institute of Science and Technology (2013-2015)

Principal Investigator

Shiosaka Sadao  大阪行岡医療大学, 公私立大学の部局等, 教授 (90127233)

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)
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)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
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)
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
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.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (5 results)

All 2017 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) Book (2 results)

  • [Journal Article] Ablation of neuropsin-neuregulin1 signaling imbalances ErbB4 inhibitory networks and disrupts hippocampal gamma oscillation2017

    • Author(s)
      Kawata M, Morikawa S, Shiosaka S Tamura H
    • Journal Title

      Translational Psychiatry

      Volume: 7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments2014

    • Author(s)
      Suzuki H, Kanagawa D, Nakazawa H, Tawara-Hirata Y, Kogure Y, Shimizu-Okabe C, Takayama C, Ishikawa Y, Shiosaka S
    • Journal Title

      Front Cell Neurosci

      Volume: 8 Pages: 420-420

    • DOI

      10.3389/fncel.2014.00420

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Unbiased search for potential substrate for proteases

    • Author(s)
      谷川美佑希、俵ー平田佳江、田村英紀、塩坂貞夫
    • Organizer
      第87回日本薬理学会年会(仙台)
    • Place of Presentation
      仙台国際センター(宮城県、仙台市)
    • Related Report
      2013 Annual Research Report
  • [Book] Synaptic Tagging and Capture2015

    • Author(s)
      Ishikawa Y and Shiosaka S
    • Total Pages
      263
    • Publisher
      Springer (Sreedharan Sajikumar Editor)
    • Related Report
      2015 Annual Research Report
  • [Book] Synaptic Tagging and Capture (S Sagikumar, Editor)2015

    • Author(s)
      Ishikawa Y and Shiosaka S
    • Total Pages
      263
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2020-08-26  

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