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Exercise‐dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF‐SRF signalling
Author(s) -
Solagna Francesca,
Nogara Leonardo,
Dyar Kenneth A.,
Greulich Franziska,
Mir Ashfaq A.,
Türk Clara,
Bock Theresa,
Geremia Alessia,
Baraldo Martina,
Sartori Roberta,
Farup Jean,
Uhlenhaut Henriette,
Vissing Kristian,
Krüger Marcus,
Blaauw Bert
Publication year - 2020
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13496
Subject(s) - serum response factor , phosphorylation , histone , transcription factor , biology , chromatin , myocardin , hedgehog signaling pathway , microbiology and biotechnology , medicine , endocrinology , signal transduction , gene , genetics
Aim Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well‐defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise. Methods We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo and treadmill running. We analysed muscle biopsies from human subjects to verify if our findings in murine muscle also translate to exercise in humans. Results We identified a new phosphorylation site on Myocardin‐Related Transcription Factor B (MRTF‐B), a co‐activator of serum response factor (SRF). Phosphorylation of MRTF‐B is required for its nuclear translocation after exercise and is accompanied by the transcription of the SRF target gene Fos . In addition, high‐intensity exercise also remodels chromatin at specific SRF target gene loci through the phosphorylation of histone 3 on serine 10 in myonuclei of both mice and humans. Ablation of the MAP kinase member MSK1/2 is sufficient to prevent this histone phosphorylation, reduce induction of SRF‐target genes, and prevent increases in protein synthesis after exercise. Conclusion Our results identify a new exercise signalling fingerprint in vivo, instrumental for exercise‐induced protein synthesis and potentially muscle growth.