HSP90 modulates the myosin replacement rate in myofibrils

Koichi Ojima, Emi Ichimura, Takahiro Suzuki, Mika Oe, Susumu Muroya, Takanori Nishimura

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Myosin is a major myofibrillar component in skeletal muscles. In myofibrils, ~300 myosin molecules form a single thick filament in which there is constant turnover of myosin. Our previous study demonstrated that the myosin replacement rate is reduced by inhibition of protein synthesis (Ojima K, Ichimura E, Yasukawa Y, Wakamatsu J, Nishimura T, Am J Physiol Cell Physiol 309: C669–C679, 2015); however, additional factors influencing myosin replacement were unknown. Here, we showed that rapid myosin replacement requires heat shock protein 90 (HSP90) activity. We utilized the fluorescence recovery after photobleaching technique to measure the replacement rate of green fluorescent protein-fused myosin heavy chain (GFP-MYH) in myotubes overexpressing HSP90. Intriguingly, the myosin replacement rate was significantly increased in HSP90-overexpressing myotubes, whereas the myosin replacement rate slowed markedly in the presence of an HSP90-specific inhibitor, indicating that HSP90 activity promotes myosin replacement. To determine the mechanism of this effect, we investigated whether HSP90 activity increased the amount of myosin available for incorporation into myofibrils. Strikingly, the gene expression levels of MYHs were significantly elevated by HSP90 overexpression but downregulated by inhibition of HSP90 activity. Cytosolic myosin content was also increased in myotubes overexpressing HSP90. Taken together, our results demonstrate that HSP90 activity facilitates myosin replacement by upregulating MYH gene expression and thereby increasing cytosolic myosin content.

Original languageEnglish
Pages (from-to)C104-C114
JournalAmerican Journal of Physiology - Cell Physiology
Volume315
Issue number1
DOIs
Publication statusPublished - Jul 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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