Microtubules tune cytoskeletal stiffness, which affects cytoskeletal mechanics and mechanotransduction of striated muscle. While recent evidence suggests that microtubules enriched in detyrosinated α-tubulin regulate these processes in healthy muscle and increase them in disease, the possible contribution from several other α-tubulin modifications has not been investigated. Here, we used genetic and pharmacologic strategies in isolated cardiomyocytes and skeletal myofibers to increase the level of acetylated α-tubulin without altering the level of detyrosinated α-tubulin. We show that microtubules enriched in acetylated α-tubulin increase cytoskeletal stiffness and viscoelastic resistance. These changes slow rates of contraction and relaxation during unloaded contraction and increased activation of NADPH oxidase 2 (Nox2) by mechanotransduction. Together, these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle in health and disease.
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Communication|
March 19 2021
Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
Andrew K. Coleman
,
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
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Humberto C. Joca
,
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
Correspondence to Humberto C. Joca: hjoca@som.umaryland.edu
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Guoli Shi
,
Guoli Shi
2
Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD
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W. Jonathan Lederer
,
W. Jonathan Lederer
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
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Christopher W. Ward
2
Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD
Christopher W. Ward: ward@umaryland.edu
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Andrew K. Coleman
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
Humberto C. Joca
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
Guoli Shi
2
Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD
W. Jonathan Lederer
1
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD
Christopher W. Ward
2
Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD
Correspondence to Humberto C. Joca: hjoca@som.umaryland.edu
Christopher W. Ward: ward@umaryland.edu
*
A.K. Coleman and H.C. Joca contributed equally to this paper.
This work is part of a special collection on myofilament function and disease.
Received:
August 14 2020
Revision Received:
January 29 2021
Accepted:
March 01 2021
Online Issn: 1540-7748
Print Issn: 0022-1295
© 2021 Coleman et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2021) 153 (7): e202012743.
Article history
Received:
August 14 2020
Revision Received:
January 29 2021
Accepted:
March 01 2021
Citation
Andrew K. Coleman, Humberto C. Joca, Guoli Shi, W. Jonathan Lederer, Christopher W. Ward; Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle. J Gen Physiol 5 July 2021; 153 (7): e202012743. doi: https://doi.org/10.1085/jgp.202012743
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