2022 Fiscal Year Final Research Report
The mechanism of myosin replacement in the thick filament of the skeletal muscle
| Project/Area Number |
19H03100
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42010:Animal production science-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
尾嶋 孝一 国立研究開発法人農業・食品産業技術総合研究機構, 畜産研究部門, 上級研究員 (60415544)
鈴木 貴弘 北海道大学, 農学研究院, 助教 (80750877)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 骨格筋 / 筋原線維 / ミオシン / アクチン / 太いフィラメント / 筋線維型 |
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the replacement mechanism of myosin molecules in thick filaments within myofibrils. We found that myosin is more frequently inserted in the tips than the rest of the thick filament when myosin is replaced in the thick filament. The combination of pulse-chase assay with FRAP directly demonstrated the presence of the recycled myosin, which is reinserted in the thick filament once released from the thick filament. Myh3 specific E3 ligase participates in myosin replacement by selecting myosin to be degraded. Ubiquitinated myosin accumulates in the cytosol rather than the myofibrils, indicating that ubiquitinated myosin is not incorporated into the thick filament and that myosin to be degraded is selected in the cytosol. LC-MS/MS analysis revealed that methylated Myh is different between ages, Myh isoforms, and fractions (myofibril/cytosol). As adding the methyl group changes the myosin hydrophobicity, methylation may influence myosin replacement.
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| Free Research Field |
筋細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
世界人口の増加や発展途上国の経済発展を背景として食肉需要は拡大しているが、家畜生産による環境負荷等が問題となっている。環境調和・持続型の効率的な食肉生産確立するためには、食肉の主体である家畜骨格筋の筋肥大・維持機構を組織・細胞レベルで理解することが重要である。本研究の成果は、骨格筋の肥大・萎縮機構の分子基盤確立に寄与するとともに，食肉生産機構の最重要部分である家畜骨格筋肥大メカニズムの解明に繋がるため，食肉科学および畜産学分野に大きく貢献する。さらに，健康医学分野ではヒトの加齢に伴う骨格筋量の減少が身体機能を低下させるサルコペニアの発症機序解明および予防法開発に繋がる。
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