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

TY - JOUR

T1 - Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling

AU - Solagna, Francesca

AU - Nogara, Leonardo

AU - Dyar, Kenneth A

AU - Greulich, Franziska

AU - Mir, Ashfaq Ali

AU - Türk, Clara

AU - Bock, Theresa

AU - Geremia, Alessia

AU - Baraldo, Martina

AU - Sartori, Roberta

AU - Farup, Jean

AU - Uhlenhaut, Henriette

AU - Vissing, Kristian

AU - Kruger, Marcus

AU - Blaauw, Bert

N1 - This article is protected by copyright. All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - exercise

KW - histone phosphorylation

KW - protein synthesis

KW - serum response factor

KW - skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=85085593674&partnerID=8YFLogxK

U2 - 10.1111/apha.13496

DO - 10.1111/apha.13496

M3 - Journal article

C2 - 32408395

SN - 1748-1708

VL - 230

JO - Acta Physiologica

JF - Acta Physiologica

IS - 1

M1 - e13496

ER -