Abstract
ABSTRACTIn response to injury, skeletal muscle stem cells (MuSCs) undergo myogenesis where they become activated, proliferate rapidly, differentiate and undergo fusion to form multinucleated myotubes. Dramatic changes in cell size, shape, metabolism and motility occur during myogenesis, which cause cellular stress and alter proteostasis. The molecular chaperone heat shock protein 70 (HSP70) maintains proteostasis by regulating protein biosynthesis and folding, facilitating transport of polypeptides across intracellular membranes and preventing stress-induced protein unfolding/aggregation. Although HSP70 overexpression can exert beneficial effects in skeletal muscle diseases and enhance skeletal muscle repair after injury, its effect on myogenesis has not been investigated. Plasmid-mediated overexpression of HSP70 did not affect the rate of C2C12 proliferation or differentiation, but the median number of myonuclei per myotube and median myotube width in differentiated C2C12 myotubes were increased with HSP70 overexpression. These findings reveal that increased HSP70 expression can promote myoblast fusion, identifying a mechanism for its therapeutic potential to enhance muscle repair after injury.This article has an associated First Person interview with the first author of the paper.
Highlights
Skeletal muscle has a remarkable ability to regenerate in response to injury due to its resident population of adult muscle stem cells (MuSCs)
We examined the subcellular localisation of Heat shock protein 70 (HSP70) in control (Fig. 1B), GFP-transfected (Fig. 1C), and GFP-HSP70-transfected (Fig. 1D) C2C12 myoblasts under control conditions and in response to heat shock for 2 h at 42°C
C2C12 cells transfected with GFP-HSP70 undergo enhanced fusion during differentiation As HSP70 overexpression had no impact on proliferation or differentiation of C2C12 myoblasts, we examined the effect on myoblast fusion and myotube formation
Summary
Skeletal muscle has a remarkable ability to regenerate in response to injury due to its resident population of adult muscle stem cells (MuSCs). MuSCs are activated, enter the cell cycle and become specified to the myogenic lineage after which they proliferate rapidly, differentiate and undergo fusion and maturation (Yin et al, 2013). *(deceased) With much sadness we report that talented research scholar Savant Thakur died on June 16, 2019 as a result of complications arising from Duchenne muscular dystrophy. Received 26 May 2020; Accepted 17 June 2020 the most well studied member of the highly conserved HSP family of molecular chaperones, protects against cellular stress and maintains proteostasis (Clerico et al, 2015; Thakur et al, 2018)
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