Sarcomeric signallig by giant muscle proteins controlling muscle growth and turnover

我们研究了控制肌肉生长的新机制，以应对工作负荷。这将有助于理解重症监护病房或某些遗传性肌肉疾病患者的肌肉丢失是如何发生的。我们身体的随意运动和心脏的泵送功能需要横纹肌的动作，之所以叫横纹肌，是因为在显微镜下看到它们非常规则的条纹图案。这些条纹是分子机器的重复图案，称为肌节。肌节由人体最大的蛋白质--肌动蛋白组成。肌肉对使用的变化反应迅速，不使用会导致肌肉损失(称为萎缩)，运动导致肌肉生长(称为肥大)。这些事件需要经常保持平衡，并且需要传感器输入工作负载。我们研究了肌动蛋白中蛋白激酶结构域的作用，以及与之相互作用的蛋白质在肌肉生长和萎缩中的作用。我们发现肌动蛋白激酶可以对机械力做出反应，这表明它在肌肉对负荷的反应中发挥了作用。我们正在使用蛋白质研究和动物模型来研究这种机械信号的机制及其在肌肉疾病中的破坏。

We investigate new mechanisms that control the growth of muscles in response to workload. This will help to understand how muscle loss occurs in patients on intensive care units or with certain genetic muscle diseases. Voluntary movement of our body, and the pumping functions of the heart require the actions of striated muscles, so called because of their extremely regular striped pattern when viewed in a microscope. These stripes are repeating patterns of molecular machines, called sarcomeres. The sarcomere is organized by the giant protein titin, the largest protein of the human body. Muscle responds rapidly to changes in use, with disuse leading to muscle loss (called atrophy) and exercise leading to muscle growth (called hypertrophy). These events need to be constantly balanced, and require input from sensors for workload. We study the role of a protein kinase domain in titin, and the proteins interacting with, in muscle growth and atrophy. We found that the titin kinase can respond to mechanical forces, suggesting it plays a role in the responses of muscle to load. We are studying the mechanism of this mechanosignalling and its disruption in muscle diseases using protein studies and animal models.