Discovery and characterization of a pressure sensation and transduction (PREST) mechanism in the presynaptic terminal in the CNS.

2021 年度 実施状況報告書

• 研究課題/領域番号: 21K15203
• 研究機関: 東京大学
• 研究代表者: UCAR HASAN 東京大学, ニューロインテリジェンス国際研究機構, 特任助教 (50748423)
• 研究期間 (年度): 2021-04-01 – 2026-03-31
• キーワード: Release probabilty / Optogenetics / iGluSnFr / Presynaptic terminal / FRET / Spine enlargement / Mechanosensation

研究実績の概要

The following article was published in Nature.
Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis. Ucar et al., Nature, 600 (December 23, 2021), pp. 686-689.
With this study we announced the mechanical transmission and the PREST mechanism in the synapse which was a milestone in the neuroscience field.
I showed that enlarging spines pushed the presynaptic terminals, and this enhanced its activity by causing an increase in the synaptic vesicle docking onto plasma membrane and an increase in the evoked glutamate release.
I also showed that fine and transient (1 min) pushing of a presynaptic terminal by a glass pipette or application of osmotic pressure (by 20 mM sucrose) were sufficient to mimic the effects of spine enlargement.
Now, I am exploring molecular machineries underlying PREST signaling.

現在までの達成度 (区分)

2: おおむね順調に進展している

理由

We have published our results in Nature.
We are exploring the molecular machineries underlying PREST mechanisms. We have promising preliminary data on some candidate machineries.
Regulation of F-actin via Arp2/3 complex seems to be important for PREST signaling. Also instead of actin scaffold, Arp2/3 activity for F-actin dynamics could be more important.

今後の研究の推進方策

I am planning to explore the interaction of F-actin dynamics with the synaptic vesicle (SV) mobilization.
I have observations that the SV clusters are mobilized upon mechanical stimulation and I want to explore the role of F-actin in this process.

研究成果

• [雑誌論文] Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis (2021)
  • 著者名/発表者名: Ucar Hasan、Watanabe Satoshi、Noguchi Jun、Morimoto Yuichi、Iino Yusuke、Yagishita Sho、Takahashi Noriko、Kasai Haruo
  • 雑誌名: Nature 巻: 600 ページ: 686～689
  • DOI: 10.1038/s41586-021-04125-7
  • 査読あり / 国際共著
• [雑誌論文] Forceful synapses reveal mechanical interactions in the brain (2021)
  • 著者名/発表者名: Haruo Kasai, Hasan Ucar, Edwin Chapman, David Rowland
  • 雑誌名: Nature 巻: Online ページ: 1476-4687
  • DOI: 10.1038/d41586-021-03516-0
  • 国際共著
• [学会発表] Mechanosensation and PREST in the presynaptic terminals (2022)
  • 著者名/発表者名: Hasan Ucar, Satoshi Watanabe, Jun Noguchi, Sho Yagishita, Yuichiro Morimoto, Noriko Takahashi, Haruo Kasai
  • 学会等名: The 45th Annual Meeting of the Japan Neuroscience Society. The 65th Annual Meeting of the Japanese Society for Neurochemistry The 32nd Annual Conference of the Japanese Neural Network Society
  • 国際学会 / 招待講演
• [学会発表] Presynaptic terminals can sense spine enlargement and mechanical pressure to provide stronger synaptic transmission (2021)
  • 著者名/発表者名: Hasan Ucar, Satoshi Watanabe, Jun Noguchi, Sho Yagishita, Yuichiro Morimoto, Noriko Takahashi, Haruo Kasai
  • 学会等名: The 44th Annual Meeting of the Japan Neuroscience Society. The 1st CJK International Meeting
  • 国際学会