Sarcomeric signallig by giant muscle proteins controlling muscle growth and turnover

我们研究控制肌肉生长的新机制，以应对工作量。这将有助于了解重症监护病房或某些遗传性肌肉疾病患者的肌肉损失是如何发生的。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，之所以这么叫是因为在显微镜下观察时它们的条纹图案非常规则。这些条纹是分子机器的重复模式，称为肌节。肌节由巨大的肌联蛋白组织，肌联蛋白是人体最大的蛋白质。肌肉对使用的变化反应迅速，废用导致肌肉损失（称为萎缩），运动导致肌肉生长（称为肥大）。这些事件需要不断平衡，并需要来自传感器的工作负载输入。我们研究肌联蛋白中蛋白激酶结构域的作用，以及与肌联蛋白相互作用的蛋白质在肌肉生长和萎缩中的作用。我们发现肌联蛋白激酶可以对机械力产生反应，这表明它在肌肉对负荷的反应中起作用。我们正在使用蛋白质研究和动物模型研究这种机械信号传导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.