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Molecular function of a synaptic adhesion molecule, SALM/Lrfn in the brain.

Research Project

Project/Area Number 15K06789
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionShiga University of Medical Science (2016-2018)
Ritsumeikan University (2015)

Principal Investigator

Morimura Naoko  滋賀医科大学, 医学部, 特任助教 (00349044)

Research Collaborator Aruga Jun  
Mishina Masami  
Hitoshi Seiji  
Yasuda Hiroki  
Yoshikawa Takeo  
Yanaga Aki  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsシナプス接着分子 / 興奮性シナプス / 可塑性 / 自閉症 / 統合失調症 / シナプスオーガナイザー / 神経発達障害 / 非ヒト霊長類 / シナプス可塑性
Outline of Final Research Achievements

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. We demonstrated that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 were decreased. And the synapses were structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments revealed that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. We also detected functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, our research indicate that Lrfn2 serves as a core synaptic components of excitatory neurons, associating with psychiatric disorders,

Academic Significance and Societal Importance of the Research Achievements

神経細胞と神経細胞との繋ぎ目であるシナプスは、記憶・学習、認知、感情、実行機能といった高次脳機能の要所であり、シナプス形成や維持機構を分子レベルで理解することは、高次脳機能を反映する『こころ』の解明につながると考えられる。近年シナプス異常と脳発達障害との関連性にも注目されており、更なる高次脳機能における分子機序解明が求められている。本研究で明らかとなったLrfn2の興奮性シナプスの分子メカニズムは、シナプス接着分子の脳機能における生理的役割を明らかにしただけでなく、『シナプス異常と発達障害』とを結びつける知見の一つとなり脳発達障害発症のメカニズム解明および新規治療法につながる成果となった。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] FGF-2 suppresses expression of nephronectin via JNK and PI3K pathways2018

    • Author(s)
      Kato Tadashi、Yamada Atsushi、Ikehata Mikiko、Yoshida Yuko、Sasa Kiyohito、Morimura Naoko、Sakashita Akiko、Iijima Takehiko、Chikazu Daichi、Ogata Hiroaki、Kamijo Ryutaro
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 5 Pages: 836-842

    • DOI

      10.1002/2211-5463.12421

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nephronectin Expression is Inhibited by Inorganic Phosphate in Osteoblasts2018

    • Author(s)
      Kato Tadashi、Yamada Atsushi、Sasa Kiyohito、Yoshimura Kentaro、Morimura Naoko、Ogata Hiroaki、Sakashita Akiko、Kamijo Ryutaro
    • Journal Title

      Calcified Tissue International

      Volume: 104 Issue: 2 Pages: 201-206

    • DOI

      10.1007/s00223-018-0484-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice2017

    • Author(s)
      Morimura Naoko、Yasuda Hiroki、Yamaguchi Kazuhiko、Katayama Kei-ichi、Hatayama Minoru、Tomioka Naoko H.、Odagawa Maya、Kamiya Akiko、Iwayama Yoshimi、Maekawa Motoko、Nakamura Kazuhiko、Matsuzaki Hideo、Tsujii Masatsugu、Yamada Kazuyuki、Yoshikawa Takeo、Aruga Jun
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 15800-15800

    • DOI

      10.1038/ncomms15800

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-1β suppresses nephronectin expression in osteoblasts via ERK1/2 and JNK2017

    • Author(s)
      Iezumi Yuka、Yamada Atsushi、Minami Erika、Ikehata Mikiko、Yoshida Yuko、Kato Tadashi、Morimura Naoko、Ogata Hiroaki、Sakashita Akiko、Iijima Takehiko、Chikazu Daichi、Kamijo Ryutaro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 1 Pages: 773-775

    • DOI

      10.1016/j.bbrc.2017.08.104

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wnt/β-catenin signaling activates nephronectin expression in osteoblasts.2017

    • Author(s)
      Ikehata M, Yamada A, Morimura N, Itose M, Suzawa T, Shirota T, Chikazu D, Kamijo R
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 484 Issue: 2 Pages: 231-234

    • DOI

      10.1016/j.bbrc.2017.01.053

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] シナプス接着分子Lrfn2/SALM1 から発達障害を考える. Lrfn2 遺伝子欠損マウスにみられた自閉症様行動と記憶機能およ びシナプス可塑性の向上2018

    • Author(s)
      守村 直子
    • Organizer
      第19回運動器科学研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Autism-like behaviors and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice2018

    • Author(s)
      Jun Aruga, Naoko Morimura, Hiroki Yasuda, Kei-ichi Katayama, Minoru Hatayama, Takeo Yoshikawa
    • Organizer
      第91回日本薬理学会年会 第18回国際薬理学・臨床薬理学会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] RNF20/BRE1a regulates proliferation and differentiation of GBM cancer stem-like cells2018

    • Author(s)
      Kenny Daun, Naoko Morimura, Toshihiro Yokoi, Kazuhiko Nozaki, Kenji Tanigaki, Seiji Hitoshi
    • Organizer
      15th Meeting of the Asian-Pacific Society For Neurochemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Autism-like behaviors and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice2017

    • Author(s)
      Morimura N., et al.
    • Organizer
      第60回日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 加齢マウスにおける不安行動の増大および海馬のシナプス分子の減少2017

    • Author(s)
      横川拓海, 守村直子, 他
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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