Blanco, Gonzalo orcid.org/0000-0003-3827-3111, Brown, Amy and Li, Xiang (2022) ZAK-beta is activated by cell compression and mediates contraction-induced MAPK signaling in muscle. EMBO Journal. e111650. ISSN 0261-4189
Abstract
echanical inputs give rise to p38- and JNK activation which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensures adaptation to exercise, muscle repair and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAK-beta is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAK-beta's ability to recognize stress fibers in cells and Z-discs in muscle fibers, when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load, and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 29 Jun 2022 15:20 |
Last Modified: | 08 Mar 2025 00:09 |
Published Version: | https://doi.org/10.15252/embj.2022111650 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.15252/embj.2022111650 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188562 |
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Description: ZAKbis activated by cellular compression andmediates contraction-induced MAP kinase signalingin skeletal muscle
Licence: CC-BY-NC-ND 2.5