TY - JOUR
T1 - The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging
AU - Matheny, Courtney J.
AU - Qadota, Hiroshi
AU - Bailey, Aaron O.
AU - Valdebenito-Silva, Silvana
AU - Oberhauser, Andres F.
AU - Benian, Guy M.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85195435440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85195435440&partnerID=8YFLogxK
U2 - 10.1091/mbc.E23-12-0488
DO - 10.1091/mbc.E23-12-0488
M3 - Article
C2 - 38809582
AN - SCOPUS:85195435440
SN - 1059-1524
VL - 35
SP - ar98
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 7
ER -