Cytoplasmic γ-actin contributes to a compensatory remodeling response in dystrophin-deficient muscle

Dystrophin mechanically links the costameric cytoskeleton and sarcolemma, yet dystrophin-deficient muscle exhibits abnormalities in cell signaling, gene expression, and contractile function that are not clearly understood. We generated new antibodies specific for cytoplasmic γ-actin and confirmed that γ-actin most predominantly localized to the sarcolemma and in a faint reticular lattice within normal muscle cells. However, we observed that γ-actin levels were increased 10-fold at the sarcolemma and within the cytoplasm of striated muscle cells from dystrophin-deficient mdx mice. Transgenic overexpression of the dystrophin homologue utrophin, or functional dystrophin constructs in mdx muscle, restored γ-actin to normal levels, whereas γ-actin remained elevated in mdx muscle expressing nonfunctional dystrophin constructs. We conclude that increased cytoplasmic γ-actin in dystrophin-deficient muscle may be a compensatory response to fortify the weakened costameric lattice through recruitment of parallel mechanical linkages. However, the presence of excessive myoplasmic γ-actin may also contribute to altered cell signaling or gene expression in dystrophin-deficient muscle.