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補体C1qによるシナプス除去機能の新規制御メカニズムの解明

Research Project

Project/Area Number 14J07587
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKeio University

Principal Investigator

鈴木 邦道  慶應義塾大学, 医学部, 特別研究員(PD)

Project Period (FY) 2014-04-25 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords補体 / シナプス除去 / C1q / AMPA受容体 / シナプス / Cerebellin
Outline of Annual Research Achievements

<補体局在の時空間制御メカニズムとシナプス除去現象>
海馬CA2や脳の局所に観察された補体C1qは、ある種の細胞外マトリックスと共局在しており、薬理学的な糖鎖構造の除去した場合やコアタンパク質の欠損マウスにおいて、脳内C1qが顕著に減弱していた。このことからC1qは特定糖鎖パターンを認識し脳内に蓄積し、時空間的に局在が制御されている可能性が示唆された。機能的意義の検討として、子宮内電子穿孔法により大脳バレル皮質の神経細胞にGFPを遺伝子導入し、免疫染色と脳透明化法を組み合わせて樹状突起の形態を三次元的に観察する実験系を確立した。定量的検討の結果、C1q欠損マウスでは樹状突起の刈り込みが野生型に比べて起こりづらいことが見出された。
<シナプス形成の制御分子>
Cbln1のNeurexin結合ドメインとNeuronal Pentraxin1のAMPA受容体結合ドメインとを繋げたキメラ分子、Cerebellin-Pentraxin (CPTX)の受容体に対する親和性について各種のNeurexinバリアントおよびAMPA受容体サブユニットを用いて網羅的に検討した。更にシナプス形成能についても各種AMPA受容体サブユニットについて検討し、いずれのサブユニットに対してもシナプス形成を生じることを明らかにした。CPTXの機能的意義について、小脳および海馬において検討した。CPTXの投与により小脳ではシナプス形成や運動機能、シナプス伝達をcbln1欠損マウスおよびGluD2欠損マウスで回復させたが、長期抑圧(LTD)を回復させなかった。一方で、アルツハイマー病モデルマウスを用いた海馬での実験では、CPTXによりシナプス伝達、長期増強(LTP)、空間認知能力を回復させた。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (3 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Int'l Joint Research] University of Oxford/Wellcome Trust Centre for Human Genetics/Division of Structural Biology(United Kingdom)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] German Center/for Neurodegenerative Diseases/Molecular Neuroplasticity(Germany)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Oxford/Wellcome Trust Centre for Human Genetics/Division of Structural Biology(United Kingdom)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Memantine reduces the production of amyloid-β peptides through modulation of amyloid precursor protein trafficking.2017

    • Author(s)
      Ito K, Tatebe, Suzuki K, Hirayama T, Hayakawa M, Kubo H, Tomita T, Makino M
    • Journal Title

      Eur J Pharmacol

      Volume: 798 Pages: 16-25

    • DOI

      10.1016/j.ejphar.2017.02.001

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A novel designer synapse connector: for the control of synapse formation and plasticity2017

    • Author(s)
      Kunimichi Suzuki, Wataru Kakegawa, Eriko Miura, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, Michisuke Yuzaki
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      浜松アクトシティ(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Scrap & Build of synapse by C1q and engineered C1q family protein2017

    • Author(s)
      Kunimichi Suzuki, Wataru Kakegawa, Eriko Miura, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, Michisuke Yuzaki
    • Organizer
      新学術領域「スクラップ&ビルドによる脳機能の動的制御」第1回班会議
    • Place of Presentation
      軽井沢プリンスホテルウエスト「浅間」(長野県軽井沢町)
    • Year and Date
      2017-03-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Complement C1q in brain: Identification of a novel putative receptor and its function2017

    • Author(s)
      Kunimichi Suzuki, Michisuke Yuzaki
    • Organizer
      新学術領域「神経糖鎖生物学」最終シンポジウム
    • Place of Presentation
      JPタワー名古屋 ホール&カンファレンス(愛知県名古屋市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] Controls of synapse formation and plasticity by the designer synapse connector2016

    • Author(s)
      Kunimichi Suzuki, Wataru Kakegawa, Eriko Miura, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, Michisuke Yuzaki
    • Organizer
      US-Japan brain research cooperative program
    • Place of Presentation
      Baltimore(USA)
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Studying microglia interaction in the process of synapse pruning in health and disease2016

    • Author(s)
      Kunimichi Suzuki, Weilun Sun, Stoyanov Stoyan
    • Organizer
      2nd “Young Glia” meeting
    • Place of Presentation
      Homburg(Germany)
    • Year and Date
      2016-05-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Does complement C1q regulate synapse pruning via binding to chondroitin sulfate proteoglycan2016

    • Author(s)
      Kunimichi Suzuki, Wataru Kakegawa, Eriko Miura, Michisuke Yuzaki
    • Organizer
      The 3rd International Symposium on Glyco-Neuroscience
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県淡路市)
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Controls of synapse formation and plasticity by the designer synapse connector2016

    • Author(s)
      Kunimichi Suzuki, Wataru Kakegawa, Eriko Miura, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, Michisuke Yuzaki
    • Organizer
      第51回慶應ニューロサイエンス研究会
    • Place of Presentation
      慶應義塾大学医学部(東京都新宿区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規の人工的シナプス接続分子、Cerebellin-Pentraxin(CPTX)を用いたシナプス形成および可塑性の制御2015

    • Author(s)
      鈴木邦道, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, 柚崎通介
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場・国際展示場(兵庫県神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] cerebellin 1 におけるneurexin結合ドメインの解析~人為的なシナプス解除法の開発を目指して2015

    • Author(s)
      岩本創哉, 鈴木邦道, 柚崎通介
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場・国際展示場(兵庫県神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “Investigation into molecular mechanism of synapse elimination mediated by complement C1q and C3”2014

    • Author(s)
      Kunimichi Suzuki, Michisuke Yuzaki
    • Organizer
      2014 Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research
    • Place of Presentation
      Honolulu, Hawaii,USA
    • Year and Date
      2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] “Investigation into molecular mechanism of synapse elimination mediated by complement C1q and C3”2014

    • Author(s)
      Kunimichi Suzuki, Michisuke Yuzaki
    • Organizer
      第8回領域班会議“Glycans in Neuroscience” (Satellite Symposium II)
    • Place of Presentation
      Honolulu, Hawaii,USA
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Modulation of synapse formation and plasticity by a novel artificial synapse connector, Cerebellin-Pentraxin (CPTX)2014

    • Author(s)
      Kunimichi Suzuki, Jonathan Elegheert, Amber Clayton, A. Radu Aricescu, Michisuke Yuzaki
    • Organizer
      Fourth Annual Conference of COST Action ECMNET
    • Place of Presentation
      ANTALYA, TURKEY
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 補体C1q, C3は正常シナプスを除去するのか?-分子機構の探索に向けて2014

    • Author(s)
      鈴木邦道、柚崎通介
    • Organizer
      第7回神経糖鎖生物学領域班会議
    • Place of Presentation
      ヤマハリゾートつま恋,静岡
    • Year and Date
      2014-05-25
    • Related Report
      2014 Annual Research Report

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Published: 2015-01-22   Modified: 2024-03-26  

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