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Analysis of a novel D-Serine signaling underlying synaptic plasticity and motor learning

Research Project

Project/Area Number 23689012
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionKeio University

Principal Investigator

KAKEGAWA WATARU  慶應義塾大学, 医学部, 講師 (70383718)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2011: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Keywords神経科学 / 生理学 / 生体分子 / アミノ酸 / シナプス
Research Abstract

In this study, we examined the functional role of a D-serine highly existing in the developing cerebella. D-Serine in the cerebellum, which was released from glial cells in a neuronal activity-dependent manner, bound to the postsynaptically-expressing delta2-type ionotropic glutamate receptors (delta2 receptors) to regulate synaptic plasticity, a molecular basis of learning and memory. Interestingly, we revealed that delta2 receptor controlled the synaptic plasticity by binding to the tyrosine phosphatase PTPMEG via its intracellular C-terminus. Thus, D-serine-delta2 signaling is a unique D-serine signaling, which may gain new insights into the glia-neuron interaction.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (29 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 12 results) Presentation (7 results) (of which Invited: 2 results) Book (4 results) Remarks (4 results)

  • [Journal Article] Cbln1 down-regulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells2014

    • Author(s)
      Ito-Ishida, A., Kakegawa, W., Kohda, K., Miura, E., Okabe, S. and M. Yuzaki
    • Journal Title

      European Journal of Neuroscience

      Volume: 39 Issue: 8 Pages: 1268-80

    • DOI

      10.1111/ejn.12487

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unlocking the secrets of the delta2 glutamate receptor: a gatekeeper for synaptic plasticity in the cerebellum.2013

    • Author(s)
      Kohda K, Kakegawa W, Yuzaki, M.
    • Journal Title

      Commun Integr Biol.

      Volume: 1;6(6) Issue: 6 Pages: e26466-e26466

    • DOI

      10.4161/cib.26466

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reevaluation of the role of parallel fiber synapses in delay eyeblink conditioning in mice using Cbln1 as a tool.2013

    • Author(s)
      Emi K, Kakegawa W, Miura E, Ito-Ishida A, Kohda K, Yuzaki M.
    • Journal Title

      Front Neural Circuits

      Volume: 7: Pages: 180-180

    • DOI

      10.3389/fncir.2013.00180

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression.2013

    • Author(s)
      Matsuda S, Kakegawa W, Budisantoso T, Nomura T, Kohda K, Yuzaki M.
    • Journal Title

      Nat Commun.

      Volume: 4 Issue: 1 Pages: 2759-2759

    • DOI

      10.1038/ncomms3759

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain.2013

    • Author(s)
      Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Tanaka M, Iwasato T, Itohara S, Furuyama K, Kawaguchi Y, Ishizaki Y, Yuzaki M, Furuichi T.
    • Journal Title

      J Neurosci.

      Volume: 33 Issue: 44 Pages: 17326-17334

    • DOI

      10.1523/jneurosci.2777-13.2013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans.2013

    • Author(s)
      Hills LB, Masri A, Konno K, Kakegawa W, Lam A-TN, Lim-Melia E, Chandy N, Hill RS, Panlow JN, Al-Saffar M, Nasir R, Stoler JM, Barkovich AJ, Watanabe M, Yuzaki M, Mochisa GH.
    • Journal Title

      Neurology

      Volume: 15;81(16) Issue: 16 Pages: 1378-86

    • DOI

      10.1212/wnl.0b013e3182a841a3

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The δ2 glutamate receptors gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites2013

    • Author(s)
      Kohda K, Kakegawa W, Yamamoto T. (6名)
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: Vol.110 Issue: 10

    • DOI

      10.1073/pnas.1218380110

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective and regulated gene expression in murine Purkinje cells by in utero electroporation2012

    • Author(s)
      Nishiyama J, Hayashi Y, Nomura T, Miura E, Kakegawa W, Yuzaki M
    • Journal Title

      Eur J Neurosci

      Volume: 36 Issue: 7 Pages: 2867-2876

    • DOI

      10.1111/j.1460-9568.2012.08203.x

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NMDA Receptor-Mediated PIP5K Activation to Produce PI(4,5)P_2 Is Essential for AMPA Receptor Endocytosis during LTD2012

    • Author(s)
      Takamitsu Unoki
    • Journal Title

      Neuron

      Volume: 73 Issue: 1 Pages: 135-148

    • DOI

      10.1016/j.neuron.2011.09.034

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebellar long-term depression requires dephosphorylation of TAEP in Purkinie cells2012

    • Author(s)
      Nomura T, Kakegawa W, Matsuda S, Kohda K, Nishiyama J, Takahashi T, Yuzaki M
    • Journal Title

      European Journal of Neuroscience

      Volume: 35 Issue: 3 Pages: 402-410

    • DOI

      10.1111/j.1460-9568.2011.07963.x

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Delta glutamate receptor2012

    • Author(s)
      Kohda, K., Kakegawa, W., Yuzaki, M.
    • Journal Title

      Encyclopedia of signaling Molecules

      Volume: (Review)(印刷中)

    • Related Report
      2011 Annual Research Report
  • [Journal Article] D-Serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor2011

    • Author(s)
      Wataru KAKEGAWA, et al
    • Journal Title

      Nature Neuroscience

      Volume: 14 Issue: 5 Pages: 603-611

    • DOI

      10.1038/nn.2791

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new rapid protocol for eyeblink conditioning to assess cerebellar motor learning2011

    • Author(s)
      Emi K, Kohda K, Kakegawa W, Narumi S, Yuzaki M
    • Journal Title

      Neurochem Res

      Volume: 36 Issue: 7 Pages: 1314-1322

    • DOI

      10.1007/s11064-010-0392-z

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hot Press:シナプス可塑性と運動学習を制御するD-Ser-デルタ2受容体シグナリング2011

    • Author(s)
      掛川渉, 柚崎通介
    • Journal Title

      細胞工学

      Volume: 10 Pages: 1072-1073

    • Related Report
      2011 Annual Research Report
  • [Presentation] The C1q complement family complements glutamatergic synapses on cerebellar Purkinje cells. (補体C1qファミリー分子による小脳プルキンエ細胞グルタミン酸シナプスの形成機能制御)2014

    • Author(s)
      掛川渉,柚﨑通介
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 記憶をささえる脳内アミノ酸の機能と制御2014

    • Author(s)
      掛川渉
    • Organizer
      資生堂-ヒューマンメタボロトームテクノロジー社共催セミナー
    • Place of Presentation
      東京
    • Year and Date
      2014-02-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 発達期におけるシナプスの形態と機能を制御する新しい分子機構2013

    • Author(s)
      掛川渉
    • Organizer
      第45回慶應ニューロサイエンス研究会
    • Place of Presentation
      東京
    • Year and Date
      2013-01-26
    • Related Report
      2013 Final Research Report
  • [Presentation] 発達期におけるシナプスの形態と機能を制御する新しい分子機構2013

    • Author(s)
      掛川渉
    • Organizer
      第45回慶應ニューロサイエンス研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] シナプス可塑性を支えるニューロン-グリア-糖鎖相互作用2011

    • Author(s)
      掛川渉
    • Organizer
      第9回日本糖鎖科学コンソーシアムシンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-11-04
    • Related Report
      2013 Final Research Report
  • [Presentation] The C1q complement family complements glutamatergic synapses on cerebellar Purkinje cells.

    • Author(s)
      掛川渉、柚崎通介
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
  • [Presentation] 記憶をささえる脳内アミノ酸の機能と制御

    • Author(s)
      掛川渉
    • Organizer
      資生堂-HMT共催セミナー
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] (脳21特集)、シナプスを形成するばかりじゃない―δ2型グルタミン酸受容体とCbln1による新しいシナプス可塑性機構2013

    • Author(s)
      掛川渉,幸田和久,柚﨑通介
    • Publisher
      金芳堂
    • Related Report
      2013 Final Research Report
  • [Book] 脳21-トランスポートソーム:トランスポーター・チャネル群の相互作用に基づく神経系の機能構築2013

    • Author(s)
      掛川渉、幸田和久、柚崎通介
    • Total Pages
      9
    • Publisher
      金芳堂
    • Related Report
      2013 Annual Research Report
  • [Book] 細胞工学、HOT PRESS-シナプス可塑性と運動学習を制御するD-セリン-δ2受容体シグナリング2011

    • Author(s)
      掛川渉,柚﨑通介
    • Publisher
      学研メディカル秀潤社
    • Related Report
      2013 Final Research Report
  • [Book] 月刊化学、運動や楽器の技能習得にかかわる特別なアミノ酸.2011

    • Author(s)
      掛川渉
    • Publisher
      化学同人
    • Related Report
      2013 Final Research Report
  • [Remarks] 柚﨑研究室HP

    • URL

      http://www.yuzaki-lab.org/

    • Related Report
      2013 Final Research Report
  • [Remarks] 柚崎研HP

    • URL

      http://www.yuzaki-lab.org/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 柚崎研HP

    • URL

      http://www.yuzaki-lab.org/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.yuzaki-lab.org/

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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