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Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle

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 contri...

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Detalles Bibliográficos
Autores principales: Coleman, Andrew K., Joca, Humberto C., Shi, Guoli, Lederer, W. Jonathan, Ward, Christopher W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988512/
https://www.ncbi.nlm.nih.gov/pubmed/33740038
http://dx.doi.org/10.1085/jgp.202012743
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author Coleman, Andrew K.
Joca, Humberto C.
Shi, Guoli
Lederer, W. Jonathan
Ward, Christopher W.
author_facet Coleman, Andrew K.
Joca, Humberto C.
Shi, Guoli
Lederer, W. Jonathan
Ward, Christopher W.
author_sort Coleman, Andrew K.
collection PubMed
description 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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spelling pubmed-79885122022-01-05 Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle Coleman, Andrew K. Joca, Humberto C. Shi, Guoli Lederer, W. Jonathan Ward, Christopher W. J Gen Physiol Communication 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. Rockefeller University Press 2021-03-19 /pmc/articles/PMC7988512/ /pubmed/33740038 http://dx.doi.org/10.1085/jgp.202012743 Text en © 2021 Coleman et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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/).
spellingShingle Communication
Coleman, Andrew K.
Joca, Humberto C.
Shi, Guoli
Lederer, W. Jonathan
Ward, Christopher W.
Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title_full Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title_fullStr Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title_full_unstemmed Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title_short Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
title_sort tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988512/
https://www.ncbi.nlm.nih.gov/pubmed/33740038
http://dx.doi.org/10.1085/jgp.202012743
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