The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging

Courtney J. Matheny, Hiroshi Qadota, Aaron O. Bailey, Silvana Valdebenito-Silva, Andres F. Oberhauser, Guy M. Benian

Research output: Contribution to journalArticlepeer-review

Abstract

C. elegans undergo age-dependent declines in muscle organization and function, similar to human sarcopenia. The chaperone UNC-45 is required to fold myosin heads after translation and is likely used for refolding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds HSP-90 and its UCS domain binds myosin heads. We observe early onset sarcopenia when UNC-45 is reduced at the beginning of adulthood. There is sequential decline of HSP-90, UNC-45, and MHC B myosin. A mutation in age-1 delays sarcopenia and loss of HSP-90, UNC-45, and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of six serines and two threonines, seven of which occur in the UCS domain. Additional expression of UNC-45 results in maintenance of MHC B myosin and suppression of A-band disorganization in old animals. Our results suggest that increased expression or activity of UNC-45 might be a strategy for prevention or treatment of sarcopenia.

Original languageEnglish (US)
Pages (from-to)ar98
JournalMolecular Biology of the Cell
Volume35
Issue number7
DOIs
StatePublished - Jul 1 2024

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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