Elucidation of mechanism underlying myofiber-type determination

• Project/Area Number: 18K19740
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Osaka University
• Principal Investigator: FUKADA So-ichiro 大阪大学, 薬学研究科, 准教授 (20432445)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 筋線維 / 遅筋 / 速筋 / モノクローナル抗体 / 骨格筋 / 発生

Outline of Final Research Achievements

The antigen recognized by the 3A11-3 antibody is probably a 150-160 kDa membrane protein localized in the cell membrane of neonatal muscle tissue. 3A11-3 antibody is IgM and does not bind to the antigen as strongly as IgG. Therefore, it is thought that the antigen could not be efficiently recovered and identified by LC-MS/MS. As mentioned above, IgM is thought to have a weak binding force, so it is possible that the antigen is dissociated by washing the resin during pull-down. In the future, we will improve the efficiency of protein extraction from the electrophoresis bands detected by silver staining and continue to identify the proteins by LC-MS/MS.

Academic Significance and Societal Importance of the Research Achievements

これまでの筋線維タイプの決定している因子は，筋原繊維を構成するミオシンやミトコンドリアタンパクなど，その殆ど全てが細胞内タンパクである。そのため，細胞表面タンパク質が，筋線維タイプにより異なる成果は，細胞外のシグナルを介して筋線維タイプが決定される可能性を示しており，学術的には非常に新規性の高い成果である。さらに，本抗原は，筋線維タイプが決定されると，その発現が低下することから，筋線維タイプの維持ではなく，その決定に関与している可能性が高い。今回は抗原の同定には至らなかったが，その同定により様々な病態で変化する筋線維タイプの変動機能回目につながる可能性が期待される。

Research Products

• [Journal Article] Role of damage and management in muscle hypertrophy: Different behaviors of muscle stem cells in regeneration and hypertrophy (2020)
  • Author(s): Fukada So-ichiro、Akimoto Takayuki、Sotiropoulos Athanassia
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Volume: 1867 Issue: 9 Pages: 118742-118742
  • DOI: 10.1016/j.bbamcr.2020.118742
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The CalcR-PKA-Yap1 Axis Is Critical for Maintaining Quiescence in Muscle Stem Cells. (2019)
  • Author(s): Zhang L, Noguchi YT, Nakayama H, Kaji T, Tsujikawa K, Ikemoto-Uezumi M, Uezumi A, Okada Y, Doi T, Watanabe S, Braun T, Fujio Y, Fukada SI.
  • Journal Title: Cell Rep Volume: 19 Issue: 8 Pages: 2154-63
  • DOI: 10.1016/j.celrep.2019.10.057
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. (2019)
  • Author(s): Fukuda S, Kaneshige A, Kaji T, Noguchi YT, Takemoto Y, Zhang L, Tsujikawa K, Kokubo H, Uezumi A, Maehara K, Harada A, Ohkawa Y, Fukada SI.
  • Journal Title: eLife Volume: 8
  • DOI: 10.7554/elife.48284
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic (2018)
  • Author(s): Gordish-Dressman H, Willmann R, Dalle Pazze L, Kreibich A, van Putten M, Heydemann A, Bogdanik L, Lutz C, Davies K, Demonbreun AR, Duan D, Elsey D, Fukada SI, et al
  • Journal Title: Journal of Neuromuscular Disease Volume: 5 Issue: 4 Pages: 407-417
  • DOI: 10.3233/jnd-180324
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 運動負荷依存的に筋線維核が増加する機構 (2021)
  • Author(s): 深田 宗一朗
  • Organizer: 第９４回日本薬理学
  • Invited
• [Presentation] Regulation of muscle stem cell in overloaded muscle (2019)
  • Author(s): So-ichiro Fukada
  • Organizer: France-Hong Kong meeting-Hong Kong, China
  • Int'l Joint Research / Invited
• [Presentation] 筋トレと幹細胞 (2019)
  • Author(s): 深田宗一朗
  • Organizer: 愛媛大学医学部 PROSセミナー
  • Invited