Skeletal muscle consists of bundles of myofibrils that act in concert to generate movement. Each myofibril is composed of repeating contractile units, known as sarcomeres, which produce force by the sliding of the myosin-rich thick filaments along the actin-rich thin filaments. Thin filaments are anchored to the Z-disks that flank the sarcomere, whereas thick filaments anchor to the M-band at the centre of the sarcomere. In contrast to the extensive research into Z-disks and the identification of skeletal myopathies that result from their disruption, little is known about the M-band.
Myomesins (MYOMs) are a family of M-band-restricted proteins that crosslink thick filaments with MYOM1, MYOM2, and MYOM3, each occupying distinct locations within the M-band. MYOMs contain repeats of highly elastic domains and is able to reversibly stretch to 2.5 times of its original length under force, and thus MYOMs are predicted to act as molecular springs at the M-band. To investigate the roles of Myoms and the M-band, we used mutant lines and morpholino injections in combination to examine myomesin function in the zebrafish. Electron microscopic analysis showed the absence of Myom1 leads to contraction-dependent loss of the M-band and thick filament misalignment, showing that Myom1 is essential for sarcomeric integrity. We also show that loss of Myom1 does not affect maximal force generation but significantly decreases swimming activity. Our results suggest the M-band act as a shock absorber at the centre of the sarcomere, and demonstrate for the first time, Myomesin-1 is crucial in maintaining structural stability of the muscle.