TY - JOUR
T1 - Cytoplasmic γ-actin contributes to a compensatory remodeling response in dystrophin-deficient muscle
AU - Hanft, Laurin M.
AU - Rybakova, Inna N.
AU - Patel, Jitandrakumar R.
AU - Rafael-Fortney, Jill A.
AU - Ervasti, James M.
PY - 2006/4/4
Y1 - 2006/4/4
N2 - 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.
AB - 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.
KW - Costamere
KW - Muscular dystrophy
KW - Sarcolemma
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U2 - 10.1073/pnas.0600980103
DO - 10.1073/pnas.0600980103
M3 - Article
C2 - 16565216
AN - SCOPUS:33645782024
SN - 0027-8424
VL - 103
SP - 5385
EP - 5390
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -