Dynamic regulation of sarcomeric actin filaments in striated muscle

Abstract

In striated muscle, the actin cytoskeleton is differentiated into myofibrils. Actin and myosin filaments are organized in sarcomeres and specialized for producing contractile forces. Regular arrangement of actin filaments with uniform length and polarity is critical for the contractile function. However, the mechanisms of assembly and maintenance of sarcomeric actin filaments in striated muscle are not completely understood. Live imaging of actin in striated muscle has revealed that actin subunits within sarcomeric actin filaments are dynamically exchanged without altering overall sarcomeric structures. A number of regulators for actin dynamics have been identified, and malfunction of these regulators often result in disorganization of myofibril structures or muscle diseases. Therefore, proper regulation of actin dynamics in striated muscle is critical for assembly and maintenance of functional myofibrils. Recent studies have suggested that both enhancers of actin dynamics and stabilizers of actin filaments are important for sarcomeric actin organization. Further investigation of the regulatory mechanism of actin dynamics in striated muscle should be a key to understanding how myofibrils develop and operate.

Fig. 1. Actin assembly and organization during myofibrillogenesis

The assembly process of myofibrils is based on the premyofibril model proposed by Sanger et al. [2006, 2010]. In premyofibrils (A), actin filaments are nonstriated and associated with the Z-bodies containing α-actinin and nonmuscle myosin filaments. At this stage, high concentrations of G-actin are present. In nascent myofibrils (B), alignment of the Z-bodies and nonmuscle myosin becomes more ordered, while actin filaments are still nonstriated. Muscle myosin is also assembled in a nonstriated manner. The ratio of G-actin to F-actin likely decreases during this transition, although a precise correlation of the assembly stages and G/F-actin ratios has not been reported. In mature myofibrils (C), actin filaments, muscle myosin filaments, and Z-bands are organized in sarcomeres. G-actin concentrations drop to ∼1% of total actin, whereas 99% of actin is present in myofibrils as F-actin. Note that size and compositions of other myofibril proteins vary in different muscle types and organisms.

Fig. 2. Regulators of actin filament dynamics in striated muscle

An actin filament is drawn with its barbed end to the left and pointed end to the right. Regulators shown above the filament can enhance actin dynamics by promoting polymerization, depolymerization, or severing. Regulators shown below the filament stabilize actin filaments.