Journal
NEUROMUSCULAR DISORDERS
Volume 23, Issue 3, Pages 243-255Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2012.11.013
Keywords
ACTA1; Act88F; Drosophila; IFM; Nemaline myopathy; Actin; Striated muscle; Muscle disease
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Funding
- White Rose University
- JCS' lab in the EU-FP6 Network of Excellence Grant 'Myores'
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Over 190 mutations in the human skeletal muscle alpha-actin gene, ACTA1 cause congenital actin myopathies. We transgenically expressed six different mutant actins, G15R, I136M, D154N, V163L, V163M and D292V in Drosophila indirect flight muscles and investigated their effects in flies that express one wild type and one mutant actin copy. All the flies were flightless, and the IFMs showed incomplete Z-discs, disorganised actin filaments and 'zebra bodies'. No differences in levels of sarcomeric protein expression were observed, but tropomodulin staining was somewhat disrupted in D164N, V163L, G15R and V163M heterozygotes. A single copy of D292V mutant actin rescued the hypercontractile phenotypes caused by TnI and TnT mutants, suggesting that the D292V mutation interferes with thin filament regulation. Our results show that expression of actin mutations homologous to those in humans in the indirect flight muscles of Drosophila disrupt sarcomere organisation, with somewhat similar phenotypes to those observed in humans. Using Drosophila to study actin mutations may help aid our understanding of congential myopathies caused by actin mutations. (C) 2012 Elsevier B.V. All rights reserved.
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