Integrative elucidation of myosin molecular transport function and warping regulatory mechanism in the inner ear stereocilia

• Project/Area Number: 20K09687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Shinshu University
• Principal Investigator: Kitajiri Shinichiro 信州大学, 医学部, 特任准教授 (00532970)
• Co-Investigator(Kenkyū-buntansha): 三輪 徹 大阪公立大学, 大学院医学研究科, 講師 (70535591) ; 岩城 光宏 国立研究開発法人理化学研究所, 生命機能科学研究センター, 客員研究員 (30432503)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: TRIOBP / 遺伝性難聴 / ミオシン / 内耳蝸牛有毛細胞 / 内耳 / 不動毛 / DNAバネ

Outline of Research at the Start

内耳有毛細胞は、その頂面に不動毛とよばれる構造を持ち、これが音刺激により物理的に振動することで音を感じる感覚細胞である。不動毛を構成するのはアクチン繊維の束であり、そこには複数の ミオシンが存在し形態形成や分子輸送に関わっている。しかしここでのミオシンの活性調節については全く明らかにされていない。本研究では、 不動毛の根に局在するアクチン束化タンパクTRIOBPの新たな役割としてミオシン活性調節 に着目するとともに分子メカニズムを明らかにする。

Outline of Final Research Achievements

Since hair cell culture was unsuccessful in mice, the animal species was changed to guinea pigs. To generate TRIOBP-1 knockdown guinea pigs, we constructed an RNA interference system elastic body. We tried to introduce Cy3-labeled DNA springs provided by our collaborators into hair cells, but due to lack of funds for experiments, we were unable to carry out further experiments.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、内耳だけに限定されない普遍的なミオシンの活性調節に新たな知見をもたらす可能性があった。

Research Products

• [Journal Article] Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss. (2020)
  • Author(s): Miyajima H, Moteki H, Day T, Nishio SY, et al
  • Journal Title: Sci Rep. Volume: 10 Issue: 1 Pages: 7056-7056
  • DOI: 10.1038/s41598-020-63690-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The use of a MITO-Porter to deliver exogenous therapeutic RNA to a mitochondrial disease’s cell with a A1555G mutation in the mitochondrial 12S rRNA gene results in an increase in mitochondrial respiratory activity (2020)
  • Author(s): Yamada Yuma、Maruyama Minako、Kita Tomoko、Usami Shin-ichi、Kitajiri Shin-ichiro、Harashima Hideyoshi
  • Journal Title: Mitochondrion Volume: 55 Pages: 134-144
  • DOI: 10.1016/j.mito.2020.09.008
  • Peer Reviewed