Abstract
Phosphorylation of the regulatory light chain (RLC) of myosin modulates cellular functions such as muscle contraction, mitosis, and cytokinesis. Phosphorylation defects are implicated in a number of diseases. Here we focus on striated muscle where changes in RLC phosphorylation relate to diseases such as hypertrophic cardiomyopathy and muscular dystrophy, or age-related changes. RLC phosphorylation in smooth muscle and non-muscle cells are covered briefly where relevant. There is much scientific interest in controlling the phosphorylation levels of RLC in vivo and in vitro in order to understand its physiological function in striated muscles. A summary of available and emerging in vivo and in vitro methods is presented. The physiological role of RLC phosphorylation and novel pathways are discussed to highlight the differences between muscle types and to gain insights into disease processes.
Highlights
Muscle contraction is driven by cyclical interaction between the thin filament protein actin and the thickH
regulatory light chain (RLC) phosphorylation enhances actomyosin interactions to accelerate myosin ATPase kinetics and force generation following calcium activation in skeletal muscle (Sweeney and Stull 1990). This is supported by structural studies which show that phosphorylation promotes the movement of the myosin heads away from the thick filament backbone resulting in the rotation of the cross-bridge/lever arm (Fig. 3) (Irving et al 2000; Ushakov et al 2011)
With regard to compensatory expression or modification of other proteins in cells carrying mutant constructs in transgenic animals, Scruggs et al found that transgenically abolishing RLC phosphorylation reduces phosphorylation of both myosin binding protein C (MyBP-C) and troponin I (TnI) in cardiac muscle (Scruggs et al 2009)
Summary
RLC phosphorylation enhances actomyosin interactions to accelerate myosin ATPase kinetics and force generation following calcium activation in skeletal muscle (Sweeney and Stull 1990) This is supported by structural studies which show that phosphorylation promotes the movement of the myosin heads away from the thick filament backbone resulting in the rotation of the cross-bridge/lever arm (Fig. 3) (Irving et al 2000; Ushakov et al 2011). Whether the effect of RLC phosphorylation is to disorder the S1’s RLC-region and S1’s myosin head domain or to just shift the equilibrium of the interaction between S1’s RLC region and thick filament backbone surface to an “ON” state (not referring to calcium activation) may depend on the type of muscle skeletal (Midde et al 2013), or cardiac (Kampourakis and Irving 2015). Strategies to control RLC phosphorylation may benefit heart function in disease
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