Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 14, Pages 5385-5390Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0600980103
Keywords
costamere; muscular dystrophy; sarcolemma
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Funding
- NHLBI NIH HHS [T32 HL007936, T32 HL 07936] Funding Source: Medline
- NIAMS NIH HHS [R01 AR049899, AR 042423, R01 AR042423, AR 049899] Funding Source: Medline
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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 gamma-actin and confirmed that gamma actin most predominantly localized to the sarcolemma and in a faint reticular lattice within normal muscle cells. However, we observed that gamma-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 gamma-actin to normal levels, whereas gamma-actin remained elevated in mdx muscle expressing nonfunctional dystrophin constructs. We conclude that increased cytoplasmic gamma-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 gamma-actin may also contribute to altered cell signaling or gene expression in dystrophin-deficient muscle.
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