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Functional analysis of MDGA family proteins on neural circuit formation of cerebral cortex.

Research Project

Project/Area Number 25460059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKagawa University

Principal Investigator

Yamamoto Tohru  香川大学, 医学部, 教授 (10251480)

Research Collaborator Craig Ann Marie  The University of British Columbia, Neurobiology Research Centre, Professor & Canada Research Chair
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自閉症スペクトラム障害 / 統合失調症 / MDGA1 / MDGA2 / Neuroligin / シナプス形成 / E/Iバランス / E/Iバランス / ニューロリギン / 自閉症スペクトラム / 行動異常 / 大脳皮質 / 自閉症 / 行動解析
Outline of Final Research Achievements

Mdga1 encodes a GPI-anchored IgSF protein, which we isolated as a gene expressed by a specific subset of neurons. In mouse coticogenesis, Mdga1 is selectively expressed by the upper layer neurons, while the other family member Mdga2 is widely expressed in a brain. We previously showed that Mdga1 is required for proper radial migration of a subset of upper-layer neurons; however, the resultant layer structure becomes apparently normal. We further investigated the function of MDGA family proteins in postnatal brain function since expression of Mdga1/2 persists throughput the life. It was shown that MDGA1/2 directly interact with Neuroligin family molecules to inhibit their binding to Neurexin, and we found that MDGA1 deficient mice showed more inhibitory synapses and MDGA2 +/- mice showed more excitatory synapses in their cortexes to exhibit behavioral abnormality related to schizophrenia or ASD, suggesting that MDGAs play an important role for maintaining proper E/I balance in a brain.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (6 results)

  • [Int'l Joint Research] The University of British Columbia(Canada)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Cincinnati Children's Hospital M.C.(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Ryanodine receptors contribute to the induction of ischemic tolerance.2016

    • Author(s)
      Nakamura-Maruyama E, Miyamoto O, Okabe N, Himi N, Feng L, Narita K, Keep RF, Yamamoto T, Nakamura T
    • Journal Title

      Brain Research Bulletin

      Volume: 122 Pages: 45-53

    • DOI

      10.1016/j.brainresbull.2016.02.018

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytoplasmic Fragment of Alcadein α Generated by Regulated Intramembrane Proteolysis Enhances Amyloid β-Protein Precursor (APP) Transport into the Late Secretory Pathway and Facilitates APP Cleavage2015

    • Author(s)
      Norio Takei, Yuriko Sobu, Ayano Kimura, Satomi Urano, Yi Piao, Yoichi Araki, Hidenori Taru, Tohru Yamamoto, Saori Hata, Tadashi Nakaya, Toshiharu Suzuki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 290 Issue: 2 Pages: 987-995

    • DOI

      10.1074/jbc.m114.599852

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased levels of plasma p3-Alcα35, a major fragment of Alcadeinα by γ-secretase cleavage, in Alzheimer's disease2014

    • Author(s)
      Omori C, Kaneko M, Nakajima E, Akatsu H, Waragai M, Maeda M, Moroshima-Kawashima M, Saito Y, Nakaya T, Taru H, Yamamoto T, Asada T, Hata S, Suzuki T. for J-ADNI
    • Journal Title

      J. Alzheimers Dis

      Volume: 39 Issue: 4 Pages: 861-870

    • DOI

      10.3233/jad-131610

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.2014

    • Author(s)
      Chiba K, Araseki M, Nozawa K, Furukori K, Araki Y, Matsushima T, Nakaya T,Hata S, Saito Y, Uchida S, Okada Y, Nairn AC, Davis RJ, Yamamoto T, Kinjo M, Taru, H, Suzuki T.
    • Journal Title

      Mol Biol Cell

      Volume: 25 Issue: 22 Pages: 3569-3580

    • DOI

      10.1091/mbc.e14-06-1111

    • NAID

      120005522339

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ameliorative effects of yokukansan on behavioral deficits in a gerbil model of global cerebral ischemia.2014

    • Author(s)
      Yanan Liu
    • Journal Title

      Brain Res.

      Volume: 1543 Pages: 300-307

    • DOI

      10.1016/j.brainres.2013.11.015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanism of intramembrane cleavage of Alcadeins by γ-secretase2013

    • Author(s)
      Piao, Y., Kimura, A., Urano, S., Saito, Y., Taru, H., Yamamoto, T., Hata, S. and Suzuki, T
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e62431-e62431

    • DOI

      10.1371/journal.pone.0062431

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] アルカデインはX11Lと協働して内在性APPのアミロイド産生的代謝を抑制する2015

    • Author(s)
      山本 融 後藤 直也 齋藤 有紀 村山 千明 鈴木 利治
    • Organizer
      第38回分子生物学会年会・第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 大脳新皮質形成時における放射状細胞移動の細胞種による多様性2015

    • Author(s)
      尾嶋 大喜 山本 融
    • Organizer
      第38回分子生物学会年会・第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] JIP1を介したAPP軸索順行輸送の制御機構解析2015

    • Author(s)
      加藤 優実 千葉 杏子 山本 融 鈴木 利治
    • Organizer
      第38回分子生物学会年会・第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Absence of MDGA1 Enhances Inhibitory Drive and Confers Resistance to Increased Excitation in Mouse Hippocampus2015

    • Author(s)
      Steven A. Connor, Ina Ammendrup-Johnsen, Parisa Karimi Tari, Tohru Yamamoto, Yu Tian Wang, and Ann Marie Craig
    • Organizer
      9th Annual Canadian Neuroscience Meeting
    • Place of Presentation
      Westin Bayshore, Vancouver, Canada
    • Year and Date
      2015-05-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Alcadein drives kinesin-1 and undergoes constitutive limited proteolysis to maintain proper distribution of kineisn-1.2014

    • Author(s)
      山本融 豊島哲彦 丸田千明 荒関雅彦 鈴木利治
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Ameliorative effects of Yokukansan on behavioral deficits following transient forebrain ischemia in gerbils2014

    • Author(s)
      劉亜南 中村丈洋 豊島哲彦 山本融 板野俊文
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2022-01-27  

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