Abstract
Muscle contractile apparatus (myofibrils) is a highly ordered structure, where actin and myosin filaments are organized in a hexagonal lattice with correct polarity and precise spatial position to generate cross-striated sarcomeric structures. They are anchored to Z- or M-lines, and supported by connectin/titin and nebulin filaments. Recently, numbers of new proteins have been reported to be involved in filament organization Therefore, regulatory mechanisms that control formation and maintenance of myofibrillar structure are complex. Here, we report our observations regarding how cofilin, C-protein and myosin-actin interaction are involved. Cofilin is an actin-binding protein that controls actin filament dynamics in a variety of cells. In muscle cells, we found that both over-expression and knockdown of cofilin with cDNA manipulation leads to disorganized actin assembly during myofibrillogenesis and disruption of actin filaments in sarcomeric structures. Thus, cofilin plays a critical role for the regulated assembly of actin in the myofibrils. C-protein is a myosin- and connectin-binding protein characteristic of striated muscles. We found that it also binds to actin filaments at the N-terminal side. Thus, C-protein is very likely involved in myofibril organization by interacting with multiple proteins. On the other hand, we verified that myosin-actin interaction is indispensable for myofibrillogenesis. Inhibitors of myosin or actin-myosin interaction such as BTS drastically suppressed myofibril assembly and caused disruption of sarcomeric structure when applied to muscle cells in culture. [J Physiol Sci. 2007;57 Suppl:S34]
