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

Autor:	Matheny CJ; Department of Pathology, Emory University, Atlanta, GA 30322., Qadota H; Department of Pathology, Emory University, Atlanta, GA 30322., Bailey AO; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550., Valdebenito-Silva S; Department of Neurobiology, University of Texas Medical Branch, Galveston, TX 77550., Oberhauser AF; Department of Neurobiology, University of Texas Medical Branch, Galveston, TX 77550., Benian GM; Department of Pathology, Emory University, Atlanta, GA 30322.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2024 Jul 01; Vol. 35 (7), pp. ar98. Date of Electronic Publication: 2024 May 29.
DOI:	10.1091/mbc.E23-12-0488
Abstrakt:	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. Competing Interests: Conflict of interest statement: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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