Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems

• DOI: 10.1073/pnas.1910549116
• Publication Date: 2019-10-08T00:36:28Z
• Authors: Amy Li; Shane R. Nelson; Sheema Rahmanseresht; Filip Braet; Anabelle S. Corna...; Samantha Beck Previs; Thomas S. O’Leary; James W. McNamara; Dilson E. Rassier; Sakthivel Sadayappan; Michael J. Previs; David M. Warshaw
• Keywords: Contractility; ITGA7

Significance Myosin-binding protein C (MyBP-C) is a critical component of the skeletal muscle sarcomere, muscle’s smallest contractile unit. MyBP-C’s importance evident by genetic mutations leading to human myopathies, such as distal arthrogryposis (i.e., club foot). However, molecular basis functional impact on contractility far from certain. Complicating matters further expression fast- and slow-type MyBP-C isoforms that depend whether or slow-twitch. Using multiscale proteomic, biophysical, mathematical modeling approaches, we defined expression, localization, modulatory capacities these distinct in rat muscles. Each isoform modulates differentially, providing capacity fine-tune mechanical performance physiological demands arise.