Sarcomeric signallig by giant muscle proteins controlling muscle growth and turnover

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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.