Leiomodin 3 and Tropomodulin 4 have overlapping functions during skeletal myofibrillogenesis

Abstract

Precise regulation of thin filament length is essential for optimal force generation during muscle contraction. The thin filament capping protein tropomodulin (Tmod) contributes to thin filament length uniformity by regulating elongation and depolymerization at thin filament ends. The Leiomodins (Lmods 1–3) are structurally related to the Tmods 1–4 and also localize to actin filament pointed ends, but in vitro biochemical studies indicate that Lmods act instead as robust nucleators. Here we examined the roles of Tmod4 and Lmod3 during Xenopus skeletal myofibrillogenesis. Loss of Tmod4 or Lmod3 resulted in severe disruption of sarcomere assembly and impaired embryonic movement. Remarkably, when Tmod4 deficient embryos were supplemented with additional Lmod3, and Lmod3 deficient embryos were supplemented with additional Tmod4, sarcomere assembly was rescued and embryonic locomotion improved. These results demonstrate for the first time that appropriate levels of both Tmod4 and Lmod3 are required for embryonic myofibrillogenesis and unexpectedly, both proteins can share redundant functions during in vivo skeletal muscle thin filament assembly. Further, these studies demonstrate the value of Xenopus for analysis of contractile protein function during de novo myofibril assembly.