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Functional involvement of the Arf6 pathway in FMPR-mediated synaptic plasticity

Research Project

Project/Area Number 25640025
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionKitasato University

Principal Investigator

SAKAGAMI Hiroyuki  北里大学, 医学部, 教授 (90261528)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsシナプス可塑性 / シナプス後肥厚部 / グルタミン酸受容体 / 低分子量GTP結合蛋白質 / エンドソーム / 脆弱X症候群 / 海馬 / スパイン / 記憶・学習 / 小胞輸送 / 低分子量G蛋白質 / 局所翻訳 / X連鎖性精神遅滞
Outline of Final Research Achievements

FMRP is involved in mGluR-dependent long-term depression through the regulation of local translation as an RNA-binding protein. The purpose of this study is to elucidate the role of the BRAG2-Arf6 pathway in the synaptic functions, particularly in mGluR-dependent endocytosis of AMPA receptor, because of the recent identification of BRAG2 mRNA as a FMRP target mRNA. Firstly, BRAG2c was found to localize at the postsynaptic density through its interaction with PSD-95. Secondly, BRAG2c was found to regulate mGluR-dependent endocytosis of AMPA receptor through its interaction with endophilin and subsequent Arf6 activation in cultured hippocampal neurons. These findings suggest the possible involvement of the BRAG2-Arf6 pathway in the FMRP-mediated synaptic plasticity.

Report

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

    (30 results)

All 2015 2014 2013 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (16 results) Remarks (2 results)

  • [Journal Article] Stimulation of Sigma-1 Receptor Ameliorates Depressive-like Behaviors in CaMKIV Null Mice.2015

    • Author(s)
      Moriguchi S, Sakagami H, Sasaki Y, Izumi H, Yabuki Y, Zhang C, Fukunaga K.
    • Journal Title

      Molecular Neurobiology

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detergent-dependent separation of postsynaptic density, membrane rafts and other subsynaptic structures from the synaptic plasma membrane of rat forebrain.2015

    • Author(s)
      Zhao L, Sakagami H, Suzuki T.
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Issue: 2 Pages: 147-162

    • DOI

      10.1111/jnc.12807

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Positive feedback of NR2B-containing NMDA receptor activity is the initial step toward visual imprinting: a model for juvenile learning.2015

    • Author(s)
      Nakamori T, Sato K, Kinoshita M, Kanamatsu T, Sakagami H, Tanaka K, Ohki-Hamazaki H.
    • Journal Title

      Journal of Neurochemistory

      Volume: 132 Issue: 1 Pages: 110-123

    • DOI

      10.1111/jnc.12954

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2.2014

    • Author(s)
      Akiyama M.他
    • Journal Title

      Nat Commun.

      Volume: 5 Issue: 1 Pages: 4744-4744

    • DOI

      10.1038/ncomms5744

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferantial localization of type I phosphatidylinositol 4-phosphate 5-kinase γ at the periactive zone of mouse photoreceptor ribbon synapses.2014

    • Author(s)
      Sakagami H, Katsumata O, Hara Y, Tamaki H, Fukaya M.
    • Journal Title

      Brain Research

      Volume: 1586 Pages: 23-33

    • DOI

      10.1016/j.brainres.2014.08.051

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] CaMKII activity is essential for improvement of memory-related behaviors by chronic rivastigmine treatment.2014

    • Author(s)
      Shigeki Moriguchi
    • Journal Title

      J Neurochem.

      Volume: 128(6) Issue: 6 Pages: 927-937

    • DOI

      10.1111/jnc.12510

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EFA6A, a gunanine nucleotide exchange factor for Arf6, interacts with sorting nexin-1 and regulates neurite outgrowth2014

    • Author(s)
      Fukaya M, Fukushima D, Hara Y, Sakagami H
    • Journal Title

      J. Neurochem

      Volume: 129 Issue: 1 Pages: 21-36

    • DOI

      10.1111/jnc.12524

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endosomal localization of FIP3/Arfophilin-1 and its involvement in dendritic formation of mouse hippocampal neurons.2014

    • Author(s)
      Yazaki Y, Hara Y, Tamaki H, Fukaya M, Sakagami H.
    • Journal Title

      Brain Research

      Volume: 1557 Pages: 55-65

    • DOI

      10.1016/j.brainres.2014.02.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina2013

    • Author(s)
      Sakagami H, Katsumata O, Hara Y, Tamaki H, Watanabe M, Harvey RJ, Fukaya M
    • Journal Title

      J. Comp. Neurol

      Volume: 521 Issue: 4 Pages: 860-876

    • DOI

      10.1002/cne.23206

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment2013

    • Author(s)
      Song N, Nakagawa S, Izumi T, Toda H, Kato A, Boku S, Inoue T, Sakagami H, Li X, Koyama T
    • Journal Title

      Int J Neuropsychopharmacol

      Volume: 16(4) Issue: 4 Pages: 803-812

    • DOI

      10.1017/s1461145712000570

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] EFA6 activates Arf6 and participates in its targeting to the Flemming body during cytokinesis2013

    • Author(s)
      Ueda T, Hanai A, Takei T, Kubo K, Ohgi M, Sakagami H, Takahashi S, Shin HW, Nakayama K
    • Journal Title

      FEBS Lett

      Volume: 583 Issue: 11 Pages: 1617-1623

    • DOI

      10.1016/j.febslet.2013.03.042

    • NAID

      120005293580

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Type I phosphatidylinositol 4-phosphate 5-kinase γ is required for neuronal migration in the mouse developing cerebral cortex2013

    • Author(s)
      Hara Y, Fukaya M, Tamaki H, Sakagami H
    • Journal Title

      Eur. J. Neurosci

      Volume: 38 Issue: 5 Pages: 2659-2671

    • DOI

      10.1111/ejn.12286

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] BRAG2c, a long C-terminal splice variant, interacts with endophilin III to mediate AMPA receptor internalization2015

    • Author(s)
      深谷昌弘、阪上洋行
    • Organizer
      第120回日本解剖学会総会・全国学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経細胞の移動における ADP-ribosylation factor 6(Arf6)の発現・機能解析2015

    • Author(s)
      原芳伸、深谷昌弘、阪上洋行
    • Organizer
      第120回日本解剖学会総会・全国学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大脳皮質脳層形成における低分子量GTP結合タンパク質Arf6の機能的役割2014

    • Author(s)
      原芳伸、阪上洋行
    • Organizer
      第102回日本解剖学会関東支部会
    • Place of Presentation
      東京医科大学病院(東京都新宿区)
    • Year and Date
      2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 海馬錐体細胞における低分子量Gタンパク質Arf6の細胞内局在解析2014

    • Author(s)
      深谷昌弘、阪上洋行
    • 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 Annual Research Report
  • [Presentation] 大脳皮質層形成における低分子量GTP結合タンパク質Arf6の機能的役割2014

    • Author(s)
      原芳伸、深谷昌弘、阪上洋行
    • 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 Annual Research Report
  • [Presentation] シナプス後肥厚部およびシナプス後部ラフト精製過程の系統的解析2014

    • Author(s)
      鈴木 龍雄,趙 麗穎,郭 維恒,阪上 洋行
    • 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 Annual Research Report
  • [Presentation] グリシントランスポーター2プロモーター駆動性Cre発現マウス系統におけるCre活性の組織学的解析2014

    • Author(s)
      柿崎 利和,阪上 洋行,崎村 建司,柳川 右千夫
    • 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 Annual Research Report
  • [Presentation] SRF転写コファクターMKL2のアイソフォーム発現と樹状突起形態制御2014

    • Author(s)
      田渕 明子,石橋 悠太,庄司 しずく,久保 友喜美,袴田 知之,宮田 智陽,佐藤 夏美,阪上 洋行,福地 守, 津田 正明
    • 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 Annual Research Report
  • [Presentation] 神経発達障害原因遺伝子CDKL5 の機能解析2014

    • Author(s)
      田中 輝幸,渡邉 紀,萩原 舞,村上 拓冬,小林 静香,真鍋 俊也,高雄 啓三,宮川 剛,深谷 昌弘,阪上 洋行,水口 雅,奥田 耕助
    • 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 Annual Research Report
  • [Presentation] スパインにおけるArf6活性化制御因子EFA6Aとsorting nexin-1との相互作用

    • Author(s)
      阪上洋行、福島大輔、深谷昌弘
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] Arf6活性調節因子BRAG2/OQSEC1のスプライスバリアント依存的なシナプス局在

    • Author(s)
      深谷昌弘、阪上洋行
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] Phosphatidylinositol 4-phosphate kinase 5γ は大脳皮質層形成において神経細胞の移動を制御する

    • Author(s)
      原芳伸、深谷昌弘、阪上洋行
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] シナプス局在からみたArf6グアニンヌクレオチド交換因子の分子多様性の機能的意義

    • Author(s)
      阪上洋行
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Arf6活性化因子EFA6Dのマウス脳における局在解析

    • Author(s)
      太田慎吾、深谷昌弘、阪上洋行
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      自治医科大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 海馬錐体細胞の棘突起内部における低分子量Gタンパク質Arf6のペリシナプス性局在

    • Author(s)
      深谷昌弘、阪上洋行
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      自治医科大学
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳層形成における低分子量GTP結合タンパク質Arf6の機能的役割

    • Author(s)
      原芳伸、阪上洋行
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      自治医科大学
    • Related Report
      2013 Research-status Report
  • [Remarks] 北里大学医学部解剖学(阪上)単位ホームページ

    • URL

      http://www.med.kitasato-u.ac.jp/~sakagami/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 北里大学医学部解剖学(阪上)単位ホームページ

    • URL

      http://www.med.kitasato-u.ac.jp/~sakagami/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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