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Regulation of Neural Network Formation by Proteoglycans

Research Project

Project/Area Number 16K07077
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

MAEDA Nobuaki  公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, プロジェクトリーダー (90202308)

Co-Investigator(Kenkyū-buntansha) 三枝 智香  公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 研究員 (00280800)
神村 圭亮  公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 主席研究員 (30529524)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヘパラン硫酸 / プロテオグリカン / 神経筋接合部 / シナプス可塑性 / グリピカン / ショウジョウバエ / オクトパミン / 神経可塑性 / 神経栄養因子 / 神経回路
Outline of Final Research Achievements

The synapses of the Drosophila larval neuromuscular junction (NMJ) serve as a model for the excitatory synapses because they are glutamatergic and show structural similarities to the excitatory synapses in the mammalian brain. We studied the functions of heparan sulfate proteoglycans (HSPGs) in the synapse formation and neural plasticity using Drosophila NMJ. By using shotgun proteomics, we identified spatzle as a novel HSPG-binding protein. Furthermore,we revealed that the experience-dependent neural plasticity of NMJ synapses, which is induced by starvation,is regulated by GPI-anchored HSPG glypican (Dlp).

Academic Significance and Societal Importance of the Research Achievements

近年、プロテオグリカンがシナプス形成やシナプス可塑性の制御に重要な役割を果たしており、その機能異常は種々の精神神経疾患の原因になることが明らかになってきた。本研究課題で我々は、ショウジョウバエモデルを用いて、ヘパラン硫酸プロテオグリカンによる新規シナプス機能制御機構を見出した。本研究成果は、ショウジョウバエを用いた統合失調症、心的外傷後ストレス障害等の疾患モデルの創出につながるものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (2 results)

  • [Journal Article] Suppression of the synaptic localization of a subset of proteins including APP partially ameliorates phenotypes of the Drosophila Alzheimer's disease model2018

    • Author(s)
      Furotani Koto、Kamimura Keisuke、Yajima Takaaki、Nakayama Minoru、Enomoto Rena、Tamura Takuya、Okazawa Hitoshi、Sone Masaki
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 9 Pages: e0204048-e0204048

    • DOI

      10.1371/journal.pone.0204048

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synaptic transmission from subplate neurons controls radial migration of neocortical neurons.2018

    • Author(s)
      Ohtaka-Maruyama Chiaki, Okamoto Mayumi, Endo Kentaro, Oshima Minori, Kaneko Noe, Yura Kei, Okado Haruo, Miyata Takaki, Maeda Nobuaki
    • Journal Title

      Science

      Volume: 360 Issue: 6386 Pages: 313-317

    • DOI

      10.1126/science.aar2866

    • NAID

      40021833055

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heparan sulfate proteoglycans in Drosophila neuromuscular development2017

    • Author(s)
      Kamimura Keisuke、Maeda Nobuaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1861 Issue: 10 Pages: 2442-2446

    • DOI

      10.1016/j.bbagen.2017.06.015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses.2016

    • Author(s)
      Sakuma C, Saito Y, Umehara T, Kamimura K, Maeda N, Mosca TJ, Miura M, Chihara T.
    • Journal Title

      Cell Rep

      Volume: 16 Issue: 9 Pages: 2289-2297

    • DOI

      10.1016/j.celrep.2016.07.066

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Wingless濃度勾配形成におけるヘパラン硫酸微細構造の機能解析2018

    • Author(s)
      神村圭亮、丸智香子、中藤博、由良敬、前田信明
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヘパラン硫酸微細構造によるWingless濃度勾配の制御2018

    • Author(s)
      丸智香子、神村圭亮、中藤博、前田信明、由良敬
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ショウジョウバエの神経筋接合部においてグリピカンはオクトパミンを介したシナプス可塑性を調節する.2017

    • Author(s)
      神村圭亮、小田嶋愛子、前田信明
    • Organizer
      第40回日本分子生物学会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Glypican regulates synaptic plasticity at the Drosophila neuromuscular junction.2017

    • Author(s)
      Kamimura Keisuke, Odajima Aiko., Maeda Nobuaki
    • Organizer
      7 Lakes Proteoglycans Conference 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] yata機能欠損によるAPPシナプス輸送特異的阻害のショウジョウバエアルツハイマー病モデル表現型への効果.2017

    • Author(s)
      風呂谷航人、神村圭亮、矢島隆明、中山実、田村拓也、前田信明、岡澤均、曽根雅紀.
    • Organizer
      第40回日本分子生物学会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ショウジョウバエの神経筋接合部においてグリピカンはシナプス可塑性を調節する2016

    • Author(s)
      神村圭亮、小田嶋愛子、前田信明
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
  • [Presentation] ショウジョウバエ神経筋接合部においてグリピカンはシナプス可塑性を調節する2016

    • Author(s)
      神村圭亮、小田嶋愛子、前田信明
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザ(高知県高知市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Glypican regulates synaptic plasticity at the drosophila neuromuscular junction2016

    • Author(s)
      Kamimura K., Odajima A., Maeda N.
    • Organizer
      Gordon Research Conference “Proteoglycans”
    • Place of Presentation
      Proctor Academy, Andover NH, USA
    • Year and Date
      2016-07-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 神経回路の形成とその発達異常のメカニズム

    • URL

      http://www.igakuken.or.jp/regeneration

    • Related Report
      2018 Annual Research Report
  • [Remarks] 神経回路の形成とその発達異常のメカニズム

    • URL

      http://www.igakuken.or.jp/regeneration/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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