Abstract
In striated muscle the extent of the overlap between actin and myosin filaments contributes to the development of force. In slow twitch muscle fibers actin filaments are longer than in fast twitch fibers, but the mechanism which determines this difference is not well understood. We hypothesized that tropomyosin isoforms Tpm1.1 and Tpm3.12, the actin regulatory proteins, which are specific respectively for fast and slow muscle fibers, differently stabilize actin filaments and regulate severing of the filaments by cofilin-2. Using in vitro assays, we showed that Tpm3.12 bound to F-actin with almost 2-fold higher apparent binding constant (Kapp) than Tpm1.1. Cofilin2 reduced Kapp of both tropomyosin isoforms. In the presence of Tpm1.1 and Tpm3.12 the filaments were longer than unregulated F-actin by 25% and 40%, respectively. None of the tropomyosins affected the affinity of cofilin-2 for F-actin, but according to the linear lattice model both isoforms increased cofilin-2 binding to an isolated site and reduced binding cooperativity. The filaments decorated with Tpm1.1 and Tpm3.12 were severed by cofilin-2 more often than unregulated filaments, but depolymerization of the severed filaments was inhibited. The stabilization of the filaments by Tpm3.12 was more efficient, which can be attributed to lower dynamics of Tpm3.12 binding to actin.
Highlights
Skeletal muscle is a heterogeneous tissue composed of various fiber types, which based on the expression of myosin heavy chain are classified as slow twitch, fast twitch, and hybrid fibers [1,2]
In the present work we studied the abilities of Tpm1.1 and Tpm3.12, tropomyosin isoforms expressed in fast and slow muscle fibers, to differentiate lengths of the actin filaments
As muscle isoform of cofilin was shown to participate in the maintenance of the length of sarcomeric actin filaments [24], we checked whether Tpm1.1 and Tpm3.12 diversify actin filament length and control binding, severing and shortening of the filament by cofilin-2
Summary
Skeletal muscle is a heterogeneous tissue composed of various fiber types, which based on the expression of myosin heavy chain are classified as slow twitch (type I), fast twitch (type IIA, IIX, IIB), and hybrid fibers [1,2]. Another protein which diverged into fast and slow isoforms is tropomyosin, an elongated coiled-coil protein, which extends along seven actin subunits and due to end-to-end interactions forms uninterrupted chains along both sides of the actin filament. This suggests that Tpm1.1 and Tpm3.12 have different regulatory properties that allow for contraction typical of slow and fast skeletal muscle fibers
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