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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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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. |
format | Online Article Text |
id | pubmed-7988512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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