| Project/Area Number |
18K08105
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | National Cardiovascular Center Research Institute (2019-2020)
Osaka University (2018) |
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Principal Investigator |
SHINTANI YASUNORI 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (20712243)
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| Co-Investigator(Kenkyū-buntansha) |
塚本 蔵 大阪大学, 生命機能研究科, 准教授 (80589151)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | AMPK / 介在板 / メカノストレス / 心臓介在板 / 微小管 |
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| Outline of Final Research Achievements |
In this study, we identified an active form of AMP-activated protein kinase (AMPK) localized at the intercalated disks in the heart, a specific cell–cell junction present between cardiomyocytes. A contractile inhibitor, MYK-461, prevented the localization of AMPK at the intercalated disks, suggesting that the localization of AMPK is regulated by mechanical stress. MYK-461 increased the individual cell area of cardiomyocytes in CLIP-170 phosphorylation-dependent manner. Moreover, heart-specific CLIP-170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated microtubules (MTs), leading to progressive decline in cardiac contraction. In conclusion, AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP-170 at the intercalated disks.
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| Academic Significance and Societal Importance of the Research Achievements |
介在板を発信源とするAMPKメカノシグナルによる心筋微小管の動的制御機構を明らかにし、その基質としてCLIPリン酸化が心疾患の病態形成に関わる可能性を示した。
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