Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling

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  • Francesca Solagna, Venetian Institute of Molecular Medicine (VIMM)
  • ,
  • Leonardo Nogara, Venetian Institute of Molecular Medicine (VIMM)
  • ,
  • Kenneth A Dyar, Helmholtz Diabetes Center (HMGU)
  • ,
  • Franziska Greulich, Helmholtz Diabetes Center (HMGU)
  • ,
  • Ashfaq Ali Mir, Helmholtz Diabetes Center (HMGU)
  • ,
  • Clara Türk, Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • ,
  • Theresa Bock, Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • ,
  • Alessia Geremia, Venetian Institute of Molecular Medicine (VIMM)
  • ,
  • Martina Baraldo, Venetian Institute of Molecular Medicine (VIMM)
  • ,
  • Roberta Sartori, Venetian Institute of Molecular Medicine (VIMM)
  • ,
  • Jean Farup
  • Henriette Uhlenhaut, Helmholtz Diabetes Center (HMGU)
  • ,
  • Kristian Vissing
  • Marcus Kruger, Department of Cardiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Heart Center Cologne, Cologne, Germany.
  • ,
  • Bert Blaauw, Venetian Institute of Molecular Medicine (VIMM)

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 signaling fingerprint in vivo, instrumental for exercise-induced protein synthesis and potentially muscle growth.

OriginalsprogEngelsk
Artikelnummere13496
TidsskriftActa Physiologica
Vol/bind230
Nummer1
Antal sider13
ISSN1748-1708
DOI
StatusUdgivet - 2020

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