Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity.

ABSTRACT: Various mutations in the structural proteins nebulin and titin that are present in human disease are known to affect the contractility of striated muscle. Loss of nebulin is associated with reduced actin filament length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive elasticity and is likely involved in length-dependent activation. Here, we sought to assess the modulation of muscle function by these sarcomeric proteins by using the computational platform muscle simulation code (MUSICO) to quantitatively separate the effects of structural changes, kinetics of cross-bridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation in thin filament length cannot by itself account for experimental observations of t

SUBMITTER: Mijailovich SM 

PROVIDER: S-EPMC6504291 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature