PDF(Pubmed)
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.
摘要：
C.线虫经历了肌肉组织和功能的年龄依赖性下降，类似于人类肌肉减少症。伴侣UNC-45需要在翻译后折叠肌球蛋白头部，并且可能用于在热或化学诱导的展开后重新折叠。UNC-45的TPR区结合Hsp90，其UCS域结合肌球蛋白头。当成年期开始时UNC-45减少时，我们观察到早发性肌少症。HSP-90、UNC-45和MHCB肌球蛋白依次下降。1岁时的突变可延迟肌肉减少症和HSP-90，UNC-45和肌球蛋白的丢失。UNC-45经历年龄依赖性磷酸化，质谱显示6个丝氨酸和2个苏氨酸的磷酸化，其中7出现在UCS域中。UNC-45的额外表达导致老年动物中MHCB肌球蛋白的维持和A带解体的抑制。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少肌症的策略。
