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Mechanosignaling pathways alter muscle structure and function by post-translational modification of existing sarcomeric proteins to optimize energy usage
Journal of Muscle Research and Cell Motility ( IF 1.8 ) Pub Date : 2021-02-17 , DOI: 10.1007/s10974-021-09596-9
Brenda Russell 1 , Christopher Solís 1
Affiliation  

A transduced mechanical signal arriving at its destination in muscle alters sarcomeric structure and function. A major question addressed is how muscle mass and tension generation are optimized to match actual performance demands so that little energy is wasted. Three cases for improved energy efficiency are examined: the troponin complex for tuning force production, control of the myosin heads in a resting state, and the Z-disc proteins for sarcomere assembly. On arrival, the regulation of protein complexes is often controlled by post-translational modification (PTM), of which the most common are phosphorylation by kinases, deacetylation by histone deacetylases and ubiquitination by E3 ligases. Another branch of signals acts not through peptide covalent bonding but via ligand interactions (e.g. Ca2+ and phosphoinositide binding). The myosin head and the regulation of its binding to actin by the troponin complex is the best and earliest example of signal destinations that modify myofibrillar contractility. PTMs in the troponin complex regulate both the efficiency of the contractile function to match physiologic demand for work, and muscle mass via protein degradation. The regulation of sarcomere assembly by integration of incoming signaling pathways causing the same PTMs or ligand binding are discussed in response to mechanical loading and unloading by the Z-disc proteins CapZ, α-actinin, telethonin, titin N-termini, and others. Many human mutations that lead to cardiomyopathy and heart disease occur in the proteins discussed above, which often occur at their PTM or ligand binding sites.



中文翻译:

机械信号通路通过对现有肌节蛋白进行翻译后修饰来改变肌肉结构和功能,以优化能量使用

到达肌肉目的地的转导机械信号会改变肌节的结构和功能。解决的一个主要问题是如何优化肌肉质量和张力产生以匹配实际的性能需求,从而浪费很少的能量。研究了提高能量效率的三种情况:用于调节力产生的肌钙蛋白复合物、在静止状态下控制肌球蛋白头以及用于肌节组装的 Z 盘蛋白。到达后,蛋白质复合物的调节通常受翻译后修饰 (PTM) 控制,其中最常见的是激酶的磷酸化、组蛋白脱乙酰酶的脱乙酰化和 E3 连接酶的泛素化。信号的另一个分支不是通过肽共价键,而是通过配体相互作用(例如 Ca 2+和磷酸肌醇结合)。肌球蛋白头及其通过肌钙蛋白复合物与肌动蛋白结合的调节是改变肌原纤维收缩性的信号目的地的最好和最早的例子。肌钙蛋白复合物中的 PTM 调节收缩功能的效率以匹配对工作的生理需求,并通过蛋白质降解调节肌肉质量。讨论了通过整合导致相同 PTM 或配体结合的传入信号通路来调节肌节装配,以响应 Z 盘蛋白 CapZ、α-肌动蛋白、telethonin、titin N-末端等的机械加载和卸载。许多导致心肌病和心脏病的人类突变发生在上述蛋白质中,这些蛋白质通常发生在它们的 PTM 或配体结合位点。

更新日期:2021-02-17
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