Unlocking the Role of sMyBP-C: A Key Player in Skeletal Muscle Development and Growth

Abstract

Skeletal muscle is the largest organ in the body, responsible for gross movement and metabolic regulation. Recently, variants in the MYBPC1 gene have been implicated in a variety of developmental muscle diseases, such as distal arthrogryposis. How MYBPC1 variants cause disease is not well understood. Here, through a collection of novel gene-edited mouse models, we define a critical role for slow myosin binding protein-C (sMyBP-C), encoded by MYBPC1, across muscle development, growth, and maintenance during prenatal, perinatal, postnatal and adult stages. Specifically, Mybpc1 knockout mice exhibited early postnatal lethality and impaired skeletal muscle formation and structure, skeletal deformity, and respiratory failure. Moreover, a conditional knockout of Mybpc1 in perinatal, postnatal and adult stages demonstrates impaired postnatal muscle growth and function secondary to disrupted actomyosin interaction and sarcomere structural integrity. These findings confirm the essential role of sMyBP-C in skeletal muscle and reveal specific functions in both prenatal embryonic musculoskeletal development and postnatal muscle growth and function.

Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle

“…2). This is similar to that observed for MyBP-H and sMyBP-C in embryonic chicken pectoralis (50), but quite different than the specific localization of MyBP-H in a single ultrastructural stripe adjacent to the M-line of adult rabbit psoas muscle (1). In addition to sharing the C-zone, our data further indicate that MyBP-H and fMyBP-C likely compete for the same binding sites.…”