Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction

Abstract

Significance Myosin-binding protein-C (MyBP-C) is a thick filament regulatory protein found exclusively in the C-zone of the A-band in the sarcomeres of vertebrate striated muscle. Cardiac, slow skeletal, and fast skeletal MyBP-C (fMyBP-C) paralogs perform different functions. All three paralogs share similar protein structures but likely differ substantially in terms of expression and function, which may serve the distinct physiologies of fast and slow muscle fibers. However, the functional role of fMyBP-C in fast skeletal muscle is completely unknown. Genetic mutations in human fMyBP-C lead to skeletal myopathies. In this study, we used knockout mice to define the molecular basis for fMyBP-C paralog diversity. We demonstrate that fMyBP-C modulates the speed and force of fast skeletal muscle contraction.