Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York.
J Appl Physiol (1985). 2019 Aug 1;127(2):608-618. doi: 10.1152/japplphysiol.01031.2018. Epub 2019 Jul 11.
The ability of myofibers to sense and respond appropriately to mechanical signals is one of the primary determinants of the skeletal muscle phenotype. In response to a change in mechanical load, muscle cells alter their protein metabolism, primarily through the regulation of protein synthesis rate. Protein synthesis rates are determined by both translation efficiency and translational capacity within the muscle. Translational capacity is strongly determined by the ribosome content of the muscle; thus the regulation of ribosomal biogenesis by mechanical inputs has been an area of recent interest. Despite the clear association between mechanical signals and changes in protein metabolism, the molecular pathways that link these events are still not fully elucidated. This review focuses on recent studies looking at how mechanosignaling impacts translational events. The role of impaired mechanotransduction in aging is discussed, as is the connection between age-dependent signaling defects and compromised ribosomal biogenesis during mechanical overload. Finally, emerging evidence suggests that the nucleus can act as a mechanosensitive element and that this mode of mechanotransduction may have an important role in skeletal muscle physiology and adaptation.
肌纤维感知和适当响应机械信号的能力是骨骼肌表型的主要决定因素之一。肌肉细胞会根据机械负荷的变化改变其蛋白质代谢，主要通过调节蛋白质合成速率来实现。蛋白质合成速率取决于肌肉中的翻译效率和翻译能力。翻译能力主要由肌肉中的核糖体含量决定；因此，机械输入对核糖体生物发生的调节一直是最近的研究热点。尽管机械信号与蛋白质代谢变化之间存在明显的关联，但将这些事件联系起来的分子途径仍未完全阐明。这篇综述重点介绍了最近研究如何探讨机械信号如何影响翻译事件。讨论了机械转导受损在衰老中的作用，以及年龄相关信号缺陷与机械超负荷时核糖体生物发生受损之间的联系。最后，新出现的证据表明，细胞核可以作为机械敏感元件，这种机械转导方式可能在骨骼肌生理学和适应中发挥重要作用。
