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Formation and regulation of excitatory synapses

Research Project

Project/Area Number 22680029
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

HAYASHI Takashi  東京大学, 医学(系)研究科(研究院), 助教 (80547472)

Project Period (FY) 2010-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2010: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywordsシナプス形成 / グルタミン酸 / 受容体 / 翻訳後修飾 / 精神疾患 / 恒常的可塑性 / スパイン / 1分子観察 / 一分子観察 / 即時型遺伝子産物
Research Abstract

Glutamate is the major excitatory neurotransmitter in the central nervous system. Through this program, we focused on the formation and the regulation of glutamatergic excitatory synapses. Our findings revealed that the localization and trafficking of ionotropic glutamate receptors are regulated by tyrosine phosphorylation and palmitoylation in excitatory synapses. In addition, we showed that RhoA-mediated signaling pathway regulates IL1RAPL1-dependent formation and stabilization of glutamatergic synapses. Mutations of IL1RAPL1 and some palmitoyl acyl transferases are associated with mental disorders, indicating the crucial role of these molecules in the proper formation and regulation of glutamatergic synapses.

Report

(4 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (29 results)

All 2013 2012 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (20 results) (of which Invited: 6 results) Book (2 results)

  • [Journal Article] DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression2013

    • Author(s)
      Thomas G.M., Hayashi T., Huganir R.L., Linden D.J.
    • Journal Title

      Journal of Neuroscience

      Volume: 33 Issue: 39 Pages: 15401-15407

    • DOI

      10.1523/jneurosci.1283-13.2013

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Smarter neuronal signaling complexes from existing components : How regulatory modifications were acquired during animal evolution2013

    • Author(s)
      Thomas G.M., Hayashi T.
    • Journal Title

      Bioessays

      Volume: 35 Issue: 11 Pages: 929-939

    • DOI

      10.1002/bies.201300076

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway2013

    • Author(s)
      Takashi Hayashi, Tomoyuki Yoshida, Moonjin Ra, Ryo Taguchi and Masayoshi Mishina
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 6 Pages: e66254-e66254

    • DOI

      10.1371/journal.pone.0066254

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Palmitoylation at two cysteine clusters on the C-terminus of GluN2A and GluN2B differentially control synaptic targeting of NMDARs2012

    • Author(s)
      Mattison H.A., Hayashi T., Barria A.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 11 Pages: e49089-e49089

    • DOI

      10.1371/journal.pone.0049089

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking2012

    • Author(s)
      Thomas G.M., Hayashi T., Chiu S.L., Chen C.M., Huganir R.L.
    • Journal Title

      Neuron

      Volume: 73 Issue: 3 Pages: 482-496

    • DOI

      10.1016/j.neuron.2011.11.021

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic scaling requires group I mGluR activation mediated by Homer1a2010

    • Author(s)
      Hu J.H., Park J.M., Park S., Xiao B., Dehoff M.H., Kim S., Hayashi T., Schwarz M.K., Huganir R.L., Seeburg P.H., Linden D.J., Worley P.F.
    • Journal Title

      Neuron

      Volume: 68 Issue: 6 Pages: 1128-1142

    • DOI

      10.1016/j.neuron.2010.11.008

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic Scaling Requires Group I mGluR Activation Mediated by Homerla2010

    • Author(s)
      Hu JH, Park JM, Park S, Xiao B, Dehoff MH, Kim S, Hayashi T, Schwarz MK, Huganir RL, Seeburg PH, Linden DJ, Worley PF
    • Journal Title

      Neuron

      Volume: 68号 Pages: 1128-1142

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] パルミトイル化修飾に伴うグルタミン酸受容体複合体のシナプス輸送制御 Palmitoylation-dependent synaptic delivery of glutamate receptor complex2013

    • Author(s)
      林 崇
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市) (ワークショップ発表)
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Mental retardation/autism spectrum disorder related gene product IL1RAPL1 regulates formation and stabilization of glutamatergic synapses2013

    • Author(s)
      Hayashi T.
    • Organizer
      US-Japan Brain Research Collaborative Program - Current Trends and Future Directions of Synaptic Plasticity Research
    • Place of Presentation
      ワシントン州立大学(米国シアトル市) (シンポジウム発表)
    • Year and Date
      2013-07-20
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 精神疾患原因遺伝子ILIRAPL1によるRhoAを介したグルタミン酸作動性シナプス制御 IL1RAPL1 regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway2013

    • Author(s)
      林 崇、吉田 知之、三品 昌美
    • Organizer
      Neuro2013(第36回日本神経科学・第56回日本神経化学会・第23回日本神経回路学会合同大会)
    • Place of Presentation
      国立京都国際会館(京都府京都市) (口頭発表)
    • Year and Date
      2013-06-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 知的障害・自閉症関連蛋白質ILIRAPLIによるRhoAを介した興奮性シナプス制御 IL1RAPL1 associated with mental retardation and autism regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway2013

    • Author(s)
      林 崇、吉田 知之、三品 昌美
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市) (口頭発表)
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] PDZ domain-containing proteins are binding partners and substrates for a specific subgroup of palmitoylacyltransferases2012

    • Author(s)
      George J., Karnam S., Hayashi T., Huganir R.L., Thomas G.M.
    • Organizer
      Biochemical Society Focused Meeting, Regulation of protein trafficking and function by palmitoylation
    • Place of Presentation
      セント・アンズカレッジ(英国オックスフォード市)
    • Year and Date
      2012-08-24
    • Related Report
      2013 Final Research Report
  • [Presentation] 知的障害・自閉症関連蛋白質IL1RAPL1による興奮性シナプスでのAMPA型グルタミン酸受容体局在・輸送機構の調節 Mental retardation/Autism spectrum disorder related gene product IL1RAPL1 regulates membrane trafficking of the AMPA receptor in glutamatergic synapses2012

    • Author(s)
      林 崇、吉田 知之、三品 昌美
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都府京都市) (口頭発表)
    • Year and Date
      2012-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 知的障害・自閉症関連蛋白質IL1RAPL1による興奮性シナプスでのAMPA型グルタミン酸受容体局在・輸送機構の調節Mental retardation/Autism spectrum disorder related gene product IL1RAPL1 regulates membrane trafficking of the AMPA receptor in glutamatergic synapses2012

    • Author(s)
      林崇、吉田知之、三品昌美
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都府京都市)(一般口頭発表)
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 翻訳後修飾によるイオンチャンネル型グルタミン酸受容体の機能制御 Post-translational protein modification and regulation of AMPA receptors and NMDA receptors2011

    • Author(s)
      林 崇
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市) (シンポジウム発表)
    • Year and Date
      2011-12-13
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 翻訳後修飾によるイオンチャンネル型グルタミン酸受容体の機能制御Post-translational protein modification and regulation of AMPA receptors and NMDA receptors2011

    • Author(s)
      林崇
    • Organizer
      第34回日本分子生物学会年会シンポジウム
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)(招待講演)
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] イオンチャンネル型グルタミン酸受容体のパルミトイル化依存的な輸送・局在制御 Post-translational palmitoylation and regulation of ionotropic glutamate receptors in neurons2011

    • Author(s)
      林 崇
    • Organizer
      第84回日本薬理学会年会 The 11th Southeast Asian Western Pacific Regional Meeting of Pharmacologists
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市) (口頭発表)
    • Year and Date
      2011-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] Palmitoylation by DHHC5/8 regulates GRIP1 dendritic targeting and AMPA-R trafficking2010

    • Author(s)
      Thomas G, Hayashi T, Chen CM, Huganir RL
    • Organizer
      Society for Neuroscience 40^<th> annual meeting
    • Place of Presentation
      サンディエゴコンベンションセンター(米国サンディエゴ市)
    • Year and Date
      2010-11-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Palmitoylation by DHHC5/8 regulates GRIP1 dendritic targeting and AMPA-R trafficking2010

    • Author(s)
      Thomas G, Hayashi T, Chen CM, Huganir RL
    • Organizer
      Society for Neuroscience 40^<th> annual meeting
    • Place of Presentation
      サンディエゴコンベンションセンター(アメリカ合衆国)
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 脂肪酸結合によるイオンチャンネル型グルタミン酸受容体の局在と輸送の新規制御機構2010

    • Author(s)
      林 崇
    • Organizer
      第123回日本薬理学会関東部会
    • Place of Presentation
      自治医科大学地域医療情報研修センター(栃木県下野市) (口頭発表)
    • Year and Date
      2010-10-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 脂肪酸結合によるイオンチャンネル型グルタミン酸受容体の局在と輸送の新規制御機構2010

    • Author(s)
      林崇
    • Organizer
      第123回日本薬理学会関東部会
    • Place of Presentation
      自治医科大学地域医療情報研修センター(栃木県下野市)(一般口頭発表)
    • Year and Date
      2010-10-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] パルミトイル化によるグルタミン酸受容体の輸送・局在制御 Post-translational palmitoylation and regulation of AMPA receptors and NMDA receptors2010

    • Author(s)
      林 崇
    • Organizer
      Neuro2010 (第33回日本神経科学・第53回日本神経化学会・第20回日本神経回路学会合同大会)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市) (シンポジウム発表)
    • Year and Date
      2010-09-04
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] パルミトイル化によるグルタミン酸受容体の輸送・局在制御Post-translational palmitoylation and regulation of AMPA receptors and NMDA receptors2010

    • Author(s)
      林崇
    • Organizer
      Neuro2010(第33回日本神経科学・第53回日本神経化学会・第20回日本神経回路学会合同大会)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)(招待講演)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] イオンチャンネル型グルタミン酸受容体のパルミトイル化依存的な輸送・局在制御Post-translational palmitoylation and regulation of ionotropic glutamate receptors in neurons2010

    • Author(s)
      林崇
    • Organizer
      第84回日本薬理学会年会The 11^<th> Southeast Asian Western Pacific Regional Meeting of Pharmacologists
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)(一般口頭発表)
    • Year and Date
      2010-03-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 精神疾患原因遺伝子IL1RAPL1によるRhoAを介したグルタミン酸作動性シナプス制御 IL1RAPL1 regulates the formation and stabilization of glutamatergic synapses of cortical neurons through RhoA signaling pathway

    • Author(s)
      林  崇、吉田 知之、三品 昌美
    • Organizer
      Neuro2013(第36回日本神経科学・第56回日本神経化学会・第23回日本神経回路学会合同大会) 一般口頭発表
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Mental retardation/autism spectrum disorder related gene product IL1RAPL1 regulates formation and stabilization of glutamatergic synapses

    • Author(s)
      林  崇
    • Organizer
      US-Japan Brain Research Collaborative Program - Current Trends and Future Directions of Synaptic Plasticity Research シンポジウム発表
    • Place of Presentation
      ワシントン州立大学(米国シアトル市)ントン州立大学(米国シアトル市)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] パルミトイル化修飾に伴うグルタミン酸受容体複合体のシナプス輸送制御 Palmitoylation-dependent synaptic delivery of glutamate receptor complex

    • Author(s)
      林  崇
    • Organizer
      第36回日本分子生物学会年会 ワークショップ発表
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 脳科学辞典、担当項目「チロシンキナーゼ」(脳科学辞典編集委員会編)2013

    • Author(s)
      林 崇
    • Related Report
      2013 Final Research Report
  • [Book] 脳科学辞典 担当項目「チロシンリン酸化」2013

    • Author(s)
      林 崇(分担執筆)
    • Total Pages
      1
    • Publisher
      脳科学辞典編集委員会編
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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