Studing the mechanism of synaptic plasticity

• Project/Area Number: 17K08541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: University of Miyazaki
• Principal Investigator: TAKAMIYA KOGO 宮崎大学, 医学部, 教授 (40283767)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グルタミン酸受容体 / シナプス可塑性 / 糖鎖修飾 / 脳・神経 / 神経科学 / 生理学

Outline of Final Research Achievements

AMPA type glutamate receptors (AMPA-R) are mainly playing in the expression of synaptic plasticity. We have been analyzing the involvement of protein modification of AMPA-R in neuronal functions. Especially we focus on N-glycosylation of AMPA-R extracellular domain. The occupancy of AMPA-R glycosylation is regulated in activity dependent manner and it regulates synaptic plasticity. Based on our results we generated knock-in mice in which the glycosylation site is modified. And we are performing elecrtophyilogical and behavioral analysis using these mice.

Academic Significance and Societal Importance of the Research Achievements

脳の主たる興奮性神経伝達機構であるグルタミン酸とその受容体であるグルタミン酸受容体の糖鎖修飾がどのように神経機能を制御しているか、その詳細はわかっていなかった。本研究により主たるりグルタミン酸受容体であるAMPA型グルタミン酸受容体の糖鎖修飾による機能調節機能が明らかとなり、それに基づくモデルマウスの作成・解析により学習・記憶や各種精神疾患への関与が明らかとなりつつある。

Research Products

• [Journal Article] Monitoring the glycosylation of AMPA (a-amino-3-hydroxy-5-methyl-4isoxazole-propionate)-type glutamate receptors using specific antibodies reveals a novel regulatory mechanism of N-glycosylation occupancy by molecular chaperones in Mice. (2020)
  • Author(s): Midorikawa R, Takakura D, Morise J, Wakazono Y, Kawasaki N, Oka S, Takamiya K.
  • Journal Title: J. Neurochem. Volume: 0 Issue: 5 Pages: 1-19
  • DOI: 10.1111/jnc.14964
  • Peer Reviewed
• [Journal Article] AMPA receptors in the synapse turnover by monomer diffusion. (2019)
  • Author(s): Morise J, Suzuki K, Kitagawa A, Wakazono Y, Takamiya K, Tsunoyama T, Nemoto Y, Takematsu H, Kusumi A, Oka S.
  • Journal Title: Nat. Commun. Volume: 10 Issue: 1 Pages: 5245-5245
  • DOI: 10.1038/s41467-019-13229-8
  • NAID: 120006769184
  • Peer Reviewed / Open Access
• [Journal Article] N-glycosylation of the AMPA-type glutamate receptor regulates cell surface expression and tetramer formation affecting channel function (2018)
  • Author(s): Munal Babu Kandel, Saki Yamamoto, Ryosuke Midorikawa, Jyoji Morise, Yoshihiko Wakazono, Shogo Oka, Kogo Takamiya
  • Journal Title: Journal of Neurochemistry Volume: 147 Issue: 6 Pages: 730-747
  • DOI: 10.1111/jnc.14565
  • Peer Reviewed
• [Journal Article] GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors. (2017)
  • Author(s): Chiu, S. L., G. H. Diering, B. Ye, K. Takamiya, C. M. Chen, Y. Jiang, T. Niranjan, C. E. Schwartz, T. Wang and R. L. Huganir
  • Journal Title: Neuron Volume: 93 Issue: 6 Pages: 1405-1419
  • DOI: 10.1016/j.neuron.2017.02.031
  • Peer Reviewed / Int'l Joint Research
• [Presentation] AMPA受容体のGluA1ホモマーのN型糖鎖修飾はシナプス可塑性に重要な役割を担う (2019)
  • Author(s): 若園佳彦
  • Organizer: 第４２回 日本神経科学会
• [Presentation] 知的障害を伴う自閉症スペクトラム障害に見られるGluA1遺伝子変異がAMPA受容体に与える影響 (2019)
  • Author(s): 内田琢
  • Organizer: 第４２回 日本神経科学会
• [Presentation] Monitoring the glycosylation of AMPA-type glutamate receptors using specific antibodies reveals a novel regulatory mechanism of N-glycosylation occupancy by molecular chaperones (2019)
  • Author(s): 緑川良介
  • Organizer: 第９２回 日本生化学会
• [Presentation] N-glycosylation of the AMPA-type glutamate receptor regulates cell surface expression and tetramer formation affecting channel function (2018)
  • Author(s): Kandel Munal Babu.
  • Organizer: 第41回日本神経科学大会
• [Presentation] AMPA型グルタミン酸受容体のN型糖鎖修飾は、4量体形成と細胞表面への移送を制御する (2017)
  • Author(s): Kandel Munal Babu
  • Organizer: 第40回日本神経科学大会