Uncovering the protein delivery mechanism in synaptic plasticity

• Project/Area Number: 18K06498
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kobe Pharmaceutical University (2020-2021); Center for Novel Science Initatives, National Institutes of Natural Sciences (2018-2019)
• Principal Investigator: Nakayama Kei 神戸薬科大学, 薬学部, 助教 (40553590)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: シナプス可塑性 / 細胞内小器官 / 微小管 / 局所翻訳 / シナプス可塑的変化 / 可塑的変化

Outline of Final Research Achievements

To test whether organelles involved in secretory pathway change their localizations during synaptic plasticity, live imaging of ER and ERGIC was performed. These organelles　accumulated in the vicinity of the stimulated-spine. Microtubules play important roles in the motility of organelles in dendritic shaft. I therefore examined whether the dynamics of microtubules is involved in the synaptic plasticity. Spines are enlarged by the treatment with Nocodazole. In contrast, stimulation-induced change in spine was suppressed by Taxol treatment. These results suggested that the dynamics of microtubules is involved in the synaptic plasticity.

Academic Significance and Societal Importance of the Research Achievements

本研究において、シナプス刺激に応じた局所翻訳の活性化と協調して細胞内小器官の局在が制御されることが明らかになった。さらに、それら細胞内小器官の局在制御に関わる微小管動態がシナプスの可塑的変化へ関与することも示唆された。シナプスの可塑的変化は記憶形成の細胞基盤であるため、これらの研究成果は、長期記憶形成機構の理解に貢献しうると期待される。

Research Products

• [Journal Article] Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior (2020)
  • Author(s): Nakayama T, Okimura K, Shen J, Guh Y-J, Tamai K, Shimada A, Minou S, Okushi Y, Shimmura T, Furukawa Y, Kadofusa N, Sato A, Nishimura T, Tanaka M, Nakayama K, Shiina N, Yamamoto N, Loudon A.S, Nishiwaki-Ohkawa T, Shinomiya A, Nabeshima T, Nakane Y, and Yoshimura T
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: - Pages: 1-10
  • DOI: 10.1073/pnas.2000278117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C-C Chemokine Receptor 5 (CCR5) Expression in the Infarct Brain of the Photothrombosis Mouse Model (2020)
  • Author(s): Hasegawa Hiroshi、Kondo Mari、Hohjoh Hirofumi、Nakayama Kei、Segi-Nishida Eri
  • Journal Title: BPB Reports Volume: 3 Issue: 6 Pages: 208-215
  • DOI: 10.1248/bpbreports.3.6_208
  • NAID: 130007958014
  • ISSN: 2434-432X
  • Peer Reviewed
• [Presentation] 光血栓性脳梗塞モデルにおけるC-Cケモカイン受容体5(CCR5)の発現誘導 (2021)
  • Author(s): 長谷川 潤、北條 寛典、近藤 真理、中山 啓、中川 公恵、瀬木-西田 恵里
  • Organizer: 日本薬学会
• [Presentation] RNA granule protein RNG105 (caprin1) regulates dendritic mRNA localization and contributes to synaptic potentiation (2019)
  • Author(s): Ohashi R, Nakayama K, Takao K, Shiina N
  • Organizer: 日本分子生物学会年会
• [Presentation] RNG105, an RNA granule-associated RNA-binding protein, regulates the structural plasticity of spine and is required for memory formation (2018)
  • Author(s): 中山啓、阿部学、山崎真弥、藤川顕寛、野田昌晴、二木啓、御子柴克彦、崎村建司、椎名伸之
  • Organizer: 第41回 日本神経科学大会
• [Presentation] RNG105/caprin1, an RNA granule protein, regulates structural spine plasticity and is required for long-term memory formation (2018)
  • Author(s): Kei Nakayama, Manabu Abe, Maya Yamazaki, Akihiro Fujikawa, Masaharu Noda, Akira Futatsugi, Katsuhiko Mikoshiba, Kenji Sakimura, Nobuyuki Shiina
  • Organizer: The 48th Society for Neuroscience Annual Meeting
  • Int'l Joint Research