Does Nebulin Make Tropomyosin Less Dynamic in Mature Myofibrils in Cross-Striated Myocytes?

Myofibrils in vertebrate cardiac and skeletal muscles are characterized by groups of proteins arranged in contractile units or sarcomeres, which consist of four major components – thin filaments, thick filaments, titin and Z-bands. The thin actin/tropomyosin-containing filaments are embedded in the Z-bands and interdigitate with the myosin-containing thick filaments aligned in A-bands. Titin is attached to the Z-band and extends upto the middle of the A-Band. In this mini review, we have addressed the mechanism of myofibril assembly as well as the dynamics and maintenance of the myofibrils in cardiac and skeletal muscle cells. Evidence from our research as well as from other laboratories favors the premyofibril model of myofibrillogenesis. This three-step model (premyofibril to nascent myofibril to mature myofibril) not only provides a reasonable mechanism for sequential interaction of various proteins during assembly of myofibrils, but also suggests why the dynamics of a thin filament protein like tropomyosin is higher in cardiac muscle than in skeletal muscles. The dynamics of tropomyosin not only varies in different muscle types (cardiac vs. skeletal), but also varies during myofibrillogenesis, for example, premyofibril versus mature myofibrils in skeletal muscle. One of the major differences in protein composition between cardiac and skeletal muscle is nebulin localized along the thin filaments (two nebulins/thin filament) of mature myofibrils in skeletal muscle cells, but which is expressed in a minimal quantity (one nebulin/50 actin filaments) in ventricular cardiomyocytes. Interestingly, nebulin is not associated with premyofibrils in skeletal muscle. Our FRAP(Fluorescence Recovery After Photobleaching) results suggest that tropomyosin is more dynamic in premyofibrils than in mature myofibrils in skeletal muscle, and also, the dynamics of tropomyosin in mature myofibrils is significantly higher in cardiac muscle compared to skeletal muscle. Our working hypothesis is that the association of nebulin in mature myofibrils renders tropomyosin less dynamic in skeletal muscle.