Five Alternative Myosin Converter Domains Influence Muscle Power, Stretch Activation, and Kinetics.
Five Alternative Myosin Converter Domains Influence Muscle Power, Stretch Activation, and Kinetics.
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五个替代肌球蛋白转换器域影响肌肉力量、伸展激活和动力学。
DOI：
10.1016/j.bpj.2017.12.045
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发表时间：
2018
影响因子：
3.4
通讯作者：
Swank,DouglasM
中科院分区：
文献类型：
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作者：
Glasheen,BernadetteM;Ramanath,Seemanti;Patel,Monica;Sheppard,Debra;Puthawala,JoyT;Riley,LaurenA;Swank,DouglasM
肌肉已经进化成为各种各样的运动提供动力。对不同能量产生至关重要的蛋白质成分是存在于肌肉中的肌球蛋白亚型。然而，肌肉的功能变异是如何由肌球蛋白结构引起的还不是很清楚。我们使用果蝇研究了转化器的影响，转化器是位于杠杆臂和催化结构域交界处的肌球蛋白结构区域，因为它的单个肌球蛋白重链基因表达五种不同的转化器版本(11a-e)。我们创建了五个转基因果蝇品系，每个品系都被迫在其间接飞行肌肉(IFM)纤维中表达一个转换版本。电子显微镜显示，转换交换没有改变肌肉的超微结构。表示除原生IFM 11a转换器之外的转换器版本(11b-e)的四行显示飞行能力降低。通常在成体阶段肌肉中发现的表达转化器的IFM纤维产生的能量是在胚胎期和幼虫期肌肉中发现的转化器纤维的2.8倍，肌肉运动速度最高可达2.2倍。对拉伸激活力产生的微小改变在改变IFM的功率输出方面只起到很小的作用。对嵌合转换纤维的正弦分析得出的肌肉表观速率常数显示，最佳肌肉振荡频率与肌球蛋白与肌动蛋白的附着动力学呈强正相关，而与脱离相关的跨桥动力学呈负相关。这表明肌球蛋白转换器至少改变了跨桥循环的两个速率常数，其中与附着和功率行程相关的动力学改变对设定肌肉振荡功率动力学的影响最大。
Muscles have evolved to power a wide variety of movements. A protein component critical to varying power generation is the myosin isoform present in the muscle. However, how functional variation in muscle arises from myosin structure is not well understood. We studied the influence of the converter, a myosin structural region at the junction of the lever arm and catalytic domain, usingDrosophilabecause its single myosin heavy chain gene expresses five alternative converter versions (11a–e). We created five transgenic fly lines, each forced to express one of the converter versions in their indirect flight muscle (IFM) fibers. Electron microscopy showed that the converter exchanges did not alter muscle ultrastructure. The four lines expressing converter versions (11b–e) other than the native IFM 11a converter displayed decreased flight ability. IFM fibers expressing converters normally found in the adult stage muscles generated up to 2.8-fold more power and displayed up to 2.2-fold faster muscle kinetics than fibers with converters found in the embryonic and larval stage muscles. Small changes to stretch-activated force generation only played a minor role in altering power output of IFM. Muscle apparent rate constants, derived from sinusoidal analysis of the chimeric converter fibers, showed a strong positive correlation between optimal muscle oscillation frequency and myosin attachment kinetics to actin, and an inverse correlation with detachment related cross-bridge kinetics. This suggests the myosin converter alters at least two rate constants of the cross-bridge cycle with changes to attachment and power stroke related kinetics having the most influence on setting muscle oscillatory power kinetics.