Department of Pathology, Emory University, Atlanta, GA 30322.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550.
Mol Biol Cell. 2024 Jul 1;35(7):ar98. doi: 10.1091/mbc.E23-12-0488. Epub 2024 May 29.
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 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.
在翻译过程中，不要添加任何其他解释或说明。
肌肉组织和功能随年龄增长而下降，与人类的肌肉减少症相似。伴侣蛋白 UNC-45 在翻译后折叠肌球蛋白头部，并且可能在热或化学诱导的解折叠后用于重折叠。UNC-45 的 TPR 区域结合 HSP-90，其 UCS 结构域结合肌球蛋白头部。当 UNC-45 在成年早期减少时，我们观察到早发性肌肉减少症。HSP-90、UNC-45 和 MHC B 肌球蛋白依次下降。突变会延迟肌肉减少症以及 HSP-90、UNC-45 和肌球蛋白的丧失。UNC-45 经历年龄依赖性磷酸化，质谱分析显示六个丝氨酸和两个苏氨酸的磷酸化，其中七个发生在 UCS 结构域中。额外表达 UNC-45 导致 MHC B 肌球蛋白的维持和老年动物 A 带紊乱的抑制。我们的结果表明，增加 UNC-45 的表达或活性可能是预防或治疗肌肉减少症的一种策略。
