Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.
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.
['Solagna|Francesca|F|', 'Nogara|Leonardo|L|', 'Dyar|Kenneth A|KA|', 'Greulich|Franziska|F|', 'Mir|Ashfaq A|AA|', 'Türk|Clara|C|', 'Bock|Theresa|T|', 'Geremia|Alessia|A|', 'Baraldo|Martina|M|', 'Sartori|Roberta|R|', 'Farup|Jean|J|', 'Uhlenhaut|Henriette|H|', 'Vissing|Kristian|K|', 'Krüger|Marcus|M|', 'Blaauw|Bert|B|0000-0002-4167-5106']
D000818:Animals D002843:Chromatin D015444:Exercise D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018482:Muscle, Skeletal D010805:Physical Conditioning, Animal D014176:Protein Biosynthesis D026362:Serum Response Factor D015398:Signal Transduction D014157:Transcription Factors
protein synthesis exercise serum response factor histone phosphorylation skeletal muscle