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

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 re-folding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds Hsp90 and its UC...

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Bibliographic Details
Published in:Molecular biology of the cell 2024-07, Vol.35 (7), p.mbcE23120488
Main Authors: Matheny, Courtney J, Qadota, Hiroshi, Bailey, Aaron O, Valdebenito-Silva, Silvana, Oberhauser, Andres F, Benian, Guy M
Format: Article
Language:English
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Summary: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 re-folding after thermally- or chemically-induced unfolding. UNC-45's TPR region binds Hsp90 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 delays sarcopenia and loss of HSP-90, UNC-45 and myosin. UNC-45 undergoes age-dependent phosphorylation, and mass spectrometry reveals phosphorylation of 6 serines and 2 threonines, 7 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.
ISSN:1059-1524
1939-4586
1939-4586
DOI:10.1091/mbc.E23-12-0488