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Regulatory mechanism of dendritic spine morphology by microRNA

Research Project

Project/Area Number 24659093
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

YAMAGATA Kanato  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 (20263262)

Co-Investigator(Kenkyū-buntansha) TANAKA Hidekazu  立命館大学, 生命科学部, 教授 (70273638)
Co-Investigator(Renkei-kenkyūsha) SUGIURA Hiroko  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, 主席基盤技術研究職員 (40162870)
YASUDA Shin  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 (20392368)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsマイクロRNA
Outline of Final Research Achievements

Various microRNAs (miRNAs) have been identified in the mammalian brain. However, there is few literature concerning how miRNA regulates dendritic spine morphology. Therefore, I tried to identify and investigate miRNA that binds to arc mRNA, which is induced by neuronal activity and localizes to dendritic spines. Overexpression of this miRNA caused thin spines in primary neurons probably by reducing arc protein levels. We next identified a ubiquitin ligase as one of arc-binding proteins. Reduction of this ubiquitin ligase also caused thin spines in neurons. Knockout of this ligase resulted in distinct post-translational modification of arc protein. These results suggest that decrement or different modification of arc protein may change dendritic spine morphology.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (39 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (23 results) (of which Invited: 4 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex2015

    • Author(s)
      Hiroko Sugiura, Shin Yasuda, Shutaro Katsurabayashi, Hiroyuki Kawano, Kentaro Endo, Kotaro Takasaki, Katsunori Iwasaki, Masumi Ichikawa, Toshiyuki Kobayashi, Okio Hino and Kanato Yamagata
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6842-6842

    • DOI

      10.1038/ncomms7842

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance.2015

    • Author(s)
      Masui K, Tanaka K, Ikegami S, Villa GR, Yang H, Yong WH, Cloughesy TF, Yamagata K, Arai N, Cavenee WK, Mischel PS.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112(30) Issue: 30 Pages: 9406-9411

    • DOI

      10.1073/pnas.1511759112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prostaglandin transporter in the rat brain: its localization and induction by lipopolysaccharide,2015

    • Author(s)
      Hosotani R, Inoue W, Takemiya T, Yamagata K, Kobayashi S, Matsumura K
    • Journal Title

      Temperature

      Volume: 2 Issue: 3 Pages: 425-435

    • DOI

      10.1080/23328940.2015.1062953

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of inflammatory mediators in the pathogenesis of epilepsy.2014

    • Author(s)
      Shimada T, Takemiya T, Sugiura H, Yamagata K
    • Journal Title

      Mediators Inflamm.

      Volume: 2014 Pages: 901902-901902

    • DOI

      10.1155/2014/901902

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.2014

    • Author(s)
      Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K.
    • Journal Title

      Sci Rep.

      Volume: 4 Issue: 1 Pages: 5155-5155

    • DOI

      10.1038/srep05155

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nicotine induces dendritic spine remodeling in cultured hippocampal neurons.2014

    • Author(s)
      Oda A^1, Yamagata K, Nakagomi S, Uejima H, Wiriyasermkul P, Ohgaki R, Nagamori S, Kanai Y, Tanaka H.
    • Journal Title

      J Neurochem.

      Volume: 128(2) Issue: 2 Pages: 246-255

    • DOI

      10.1111/jnc.12470

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective function of 14-3-3 proteins in neurodegeneration.2013

    • Author(s)
      Shimada, T., Fournier, A.E., and Yamagata, K.
    • Journal Title

      BioMed. Res. Int.

      Volume: 2013 Pages: 564534-564534

    • DOI

      10.1155/2013/564534

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuritin: A therapeutic candidate for promoting axonal regeneration.2013

    • Author(s)
      Shimada, T., Sugiura, H., and Yamagata K.
    • Journal Title

      World J. Neurol.

      Volume: 3 Issue: 4 Pages: 138-143

    • DOI

      10.5316/wjn.v3.i4.138

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Variation in EAE scores in a mouse model of multiple sclerosis.2013

    • Author(s)
      Takeuchi, C., Yamagata, K., and Takemiya, T.
    • Journal Title

      World J. Neurol.

      Volume: 3 Issue: 3 Pages: 56-61

    • DOI

      10.5316/wjn.v3.i3.56

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 神経活動によるスパイン形態制御と脳疾患2013

    • Author(s)
      山形要人、杉浦弘子、安田 新
    • Journal Title

      日本薬理学雑誌

      Volume: 142 Pages: 106-111

    • NAID

      10031196209

    • Related Report
      2013 Research-status Report
  • [Journal Article] Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis.2013

    • Author(s)
      Takeuchi C, Matsumoto Y, Kohyama K, Uematsu S, Akira S, Yamagata K and Takemiya T.
    • Journal Title

      Neurochem Int.

      Volume: 62 Issue: 3 Pages: 271-280

    • DOI

      10.1016/j.neuint.2012.12.007

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intercellular Signaling Pathway among Endothelia, Astrocytes and Neurons in Excitatory Neuronal Damage.2013

    • Author(s)
      Takemiya T, Yamagata K.
    • Journal Title

      Int J Mol Sci.

      Volume: 14 Issue: 4 Pages: 8345-57

    • DOI

      10.3390/ijms14048345

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 過剰興奮後に生じるスパインが減少するメカニズム2012

    • Author(s)
      安田 新、杉浦弘子、山形要人
    • Journal Title

      日本薬理学雑誌

      Volume: 140 Pages: 141-141

    • Related Report
      2012 Research-status Report
  • [Presentation] TSCモデル動物を用いた基礎研究:てんかん・精神遅滞の新しいメカニズム2015

    • Author(s)
      山形要人
    • Organizer
      Tsc Meet The Experts
    • Place of Presentation
      東京ミッドタウン(東京都港区)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] てんかんモデル動物の作製と新しい治療薬の探索2015

    • Author(s)
      山形要人
    • Organizer
      第5回都医学研シンポジウム「てんかん研究の最前線」
    • Place of Presentation
      一橋講堂(東京都千代田区)
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] Neuritin mediates activity-dependent branch formation through FGF signaling2015

    • Author(s)
      Shimada T, Yoshida T, Yamagata K
    • Organizer
      第49回日本てんかん学会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex2015

    • Author(s)
      Yasuda S, Sugiura H, Katsurabayashi S, Kawano H, Endo K, Takasaki K, Iwasaki K, Ichikawa M, Kobayashi T, Hino O, Yamagata K
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティ(埼玉県さいたま市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] てんかん・精神遅滞の新しいメカニズムと治療薬の探索2015

    • Author(s)
      山形要人
    • Organizer
      第17回応用薬理シンポジウム
    • Place of Presentation
      新潟大学(新潟県新潟市)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マウスの記憶学習機能におけるInterleukin-1の週令依存的作用2015

    • Author(s)
      竹宮孝子、文沢久美、山形要人
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 結節性硬化症におけるmTORC1非依存的スパイン形態制御2014

    • Author(s)
      山形要人、安田新、杉浦弘子、島田忠之、桂林秀太郎、岩崎克典、小林敏之、樋野興夫
    • Organizer
      第131回日本薬理学会関東部会
    • Place of Presentation
      横浜市立大学(神奈川県横浜市)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Novel mechanism for the pathogenesis of tuberous sclerosis complex.2014

    • Author(s)
      Yamagata K, Sugiura H, Yasuda S, Shimada T, Katsurabayashi S, Takemiya T, Iwasaki K, Kobayashi T, Hino O
    • Organizer
      第48回日本てんかん学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2014-10-02 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.2014

    • Author(s)
      Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
    • Place of Presentation
      奈良県文化会館(奈良県奈良市)
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Neuritin induces activity-dependent axonal branch formation through FGF signaling.2014

    • Author(s)
      Shimada T, Yoshida T, and Yamagata K
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Neuritin mediates activity-dependent axonal branching in hippocampal granule cells.2014

    • Author(s)
      Shimada T, Yoshida T and Yamagata K.
    • Organizer
      Joint Meeting of the 20th Biennial Meeting of the International Society for Developmental Neuroscience and the 5th Annual NeuroDevNet Brain Development Conference
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2014-07-19 – 2014-07-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Activity-dependent axonal branching mediated by neuritin.

    • Author(s)
      Tadayuki Shimada, Tomoyuki Yoshida, and Kanato Yamagata
    • Organizer
      New Frontier of Molecular Neuropathology 2014
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Neuritin induces activity-dependent axonal branching in hippocampal granule cells.

    • Author(s)
      Tadayuki Shimada, Tomoyuki Yoshida, and Kanato Yamagata
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] An mTOR-independent mechanism for impaired spinogenesis and behavioral deficits in a rodent model of tuberous sclerosis.

    • Author(s)
      Shin Yasuda, Hiroko Sugiura, Shutaro Katsurabayashi, Katsunori Iwasaki, Toshiyuki Kobayashi, Okio Hino, Kanato Yamagata
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis.

    • Author(s)
      Takako Takemiya, Chisen Takeuchi, Kanato Yamagata.
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Neuritin induces activity-dependent axonal branching in hippocampal granule cells.

    • Author(s)
      Tadayuki Shimada, Tomoyuki Yoshida, and Kanato Yamagata
    • Organizer
      第47回日本てんかん学会
    • Place of Presentation
      北九州
    • Related Report
      2013 Research-status Report
  • [Presentation] プロトカドヘリン情報伝達系と脳の病態

    • Author(s)
      山形要人
    • Organizer
      第86回日本生化学会大会シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Roles of activity-regulated proteins in dendritic spine abnormalities

    • Author(s)
      Yamagata K
    • Organizer
      International synapse research workshop 2012 “Understanding of synapse pathology, from genome mutation to functional defects”
    • Place of Presentation
      Okazaki
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] カイニン酸処理により誘導されるGPIアンカー型蛋白質Neuritinは海馬神経細胞の異常な軸索発芽に関与する

    • Author(s)
      島田忠之 吉田知之 山形要人
    • Organizer
      第46回日本てんかん学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Novel mechanism for dendritic spine abnormality in tuberous sclerosis

    • Author(s)
      Yasuda S, Sugiura H, Katsurabayashi S, Iwasaki K, Hino O and Yamagata K
    • Organizer
      The 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] 結節性硬化症におけるスパイン形成不全の分子メカニズム

    • Author(s)
      山形要人 杉浦弘子 安田新 桂林秀太郎 高崎浩太郎 岩崎克典 樋野興夫
    • Organizer
      第63回日本薬理学会北部会
    • Place of Presentation
      新潟
    • Related Report
      2012 Research-status Report
  • [Presentation] 多発性硬化症における膜型プロスタグランジン合成酵素(mPGES-1)の関与

    • Author(s)
      竹宮孝子 竹内千仙 山形要人
    • Organizer
      第127回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 活動依存的発現分子によるシナプス形成制御と病態

    • Author(s)
      山形要人
    • Organizer
      第86回日本薬理学会年会シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] Mek3 in Encyclopedia of Signaling Molecules2012

    • Author(s)
      Yasuda S, Sugiura H and Yamagata K
    • Publisher
      Springer
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 精神・神経疾患モデル動物2013

    • Inventor(s)
      平成25年9月11日
    • Industrial Property Rights Holder
      平成25年9月11日
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-11
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] スパイン形成異常を抑制するための医薬組成物2012

    • Inventor(s)
      山形要人 杉浦弘子 安田新
    • Industrial Property Rights Holder
      山形要人 杉浦弘子 安田新
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-09-07
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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