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.
Tubulin acetylation increases cytoskeletal stiffness to regulate mechanotransduction in striated muscle
This work is part of a special collection on myofilament function and disease.
- Views Icon Views
- Share Icon Share
- Search Site
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
Download citation file: