Muscles from six fruit flies with different genetic backgrounds. Image credit: González-Morales et al. (CC BY 4.0)
Muscles are made up of many long muscle fibers, each containing thousands of cylindrical segments called sarcomeres. When animals move, proteins in the sarcomere move past each other, shortening the muscles. Inside each muscle, all sarcomeres have the same length and diameter. The protein titin controls the length of each sarcomere, but it was unknown what controls the diameter.
At the end of each sarcomere is a structure called the Z-disc that is composed of many muscle proteins. Mutations in Z-disc proteins are often involved in diseases called myopathies, where muscle structure breaks down. As the size of the Z-disc determines sarcomere diameter, improper regulation of sarcomere diameter could contribute to myopathies. One Z-disc protein called Zasp is a candidate for controlling diameter and can have many different forms in the same cells. Zasp has a similar role in most animals including humans, mice and flies.
González-Morales et al. investigated Zasp in the muscles of the fruit fly, Drosophila melanogaster. Gene editing was used to vary the amounts of different forms of Zasp inside the muscles. The results revealed two types of Zasp, those that make sarcomeres wider, and those that limit growth. Reducing the second type of Zasp resulted in bigger Z-discs and in muscle aggregates similar to the ones seen in patients with certain myopathies.
This study reveals a mechanism for coordinating the development of muscle. It also reveals the likely cause of certain myopathies and suggests a possible target for future treatment through regulation of Zasp proteins.
