Formation and regulation of excitatory synapses

• Project/Area Number: 22680029
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Smarter neuronal signaling complexes from existing components : How regulatory modifications were acquired during animal evolution (2013)
  • Author(s): Thomas G.M., Hayashi T.
  • Journal Title: Bioessays Volume: 35 Issue: 11 Pages: 929-939
  • DOI: 10.1002/bies.201300076
  • 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 pathway (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Palmitoylation at two cysteine clusters on the C-terminus of GluN2A and GluN2B differentially control synaptic targeting of NMDARs (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Homeostatic scaling requires group I mGluR activation mediated by Homer1a (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Homeostatic Scaling Requires Group I mGluR Activation Mediated by Homerla (2010)
  • 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
  • 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 complex (2013)
  • 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
  • Invited
• [Presentation] Mental retardation/autism spectrum disorder related gene product IL1RAPL1 regulates formation and stabilization of glutamatergic synapses (2013)
  • 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
  • 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 pathway (2013)
  • 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
• [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 pathway (2013)
  • 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
• [Presentation] PDZ domain-containing proteins are binding partners and substrates for a specific subgroup of palmitoylacyltransferases (2012)
  • 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
• [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 synapses (2012)
  • 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
• [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 synapses (2012)
  • 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
• [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 receptors (2011)
  • 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
  • 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 receptors (2011)
  • 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
• [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 neurons (2011)
  • 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
• [Presentation] Palmitoylation by DHHC5/8 regulates GRIP1 dendritic targeting and AMPA-R trafficking (2010)
  • 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
• [Presentation] Palmitoylation by DHHC5/8 regulates GRIP1 dendritic targeting and AMPA-R trafficking (2010)
  • 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
• [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
• [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
• [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 receptors (2010)
  • 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
  • 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 receptors (2010)
  • 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
• [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 neurons (2010)
  • 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
• [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）
• [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）
  • 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）
  • 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
• [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