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The PERK arm of the unfolded protein response regulates satellite cell-mediated skeletal muscle regeneration
- Source :
- eLife, Vol 6 (2017), eLife
- Publication Year :
- 2017
- Publisher :
- eLife Sciences Publications Ltd, 2017.
-
Abstract
- Regeneration of skeletal muscle in adults is mediated by satellite stem cells. Accumulation of misfolded proteins triggers endoplasmic reticulum stress that leads to unfolded protein response (UPR). The UPR is relayed to the cell through the activation of PERK, IRE1/XBP1, and ATF6. Here, we demonstrate that levels of PERK and IRE1 are increased in satellite cells upon muscle injury. Inhibition of PERK, but not the IRE1 arm of the UPR in satellite cells inhibits myofiber regeneration in adult mice. PERK is essential for the survival and differentiation of activated satellite cells into the myogenic lineage. Deletion of PERK causes hyper-activation of p38 MAPK during myogenesis. Blocking p38 MAPK activity improves the survival and differentiation of PERK-deficient satellite cells in vitro and muscle formation in vivo. Collectively, our results suggest that the PERK arm of the UPR plays a pivotal role in the regulation of satellite cell homeostasis during regenerative myogenesis. DOI: http://dx.doi.org/10.7554/eLife.22871.001
- Subjects :
- 0301 basic medicine
PERK
endocrine system
XBP1
Satellite Cells, Skeletal Muscle
Mouse
QH301-705.5
Science
Protein Serine-Threonine Kinases
Biology
survival
General Biochemistry, Genetics and Molecular Biology
Mice
eIF-2 Kinase
03 medical and health sciences
skeletal muscle regeneration
medicine
Animals
Regeneration
Myocyte
Biology (General)
Muscle, Skeletal
satellite cells
General Immunology and Microbiology
ATF6
Myogenesis
General Neuroscience
Endoplasmic reticulum
Membrane Proteins
Skeletal muscle
Cell Biology
General Medicine
Cell biology
Developmental Biology and Stem Cells
030104 developmental biology
medicine.anatomical_structure
Unfolded Protein Response
Unfolded protein response
Medicine
ER Stress
Stem cell
IRE1/XBP1
Research Article
Subjects
Details
- Language :
- English
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....326507ab01bfaf979e20a5bb78c72c6e