Salvi, Sheetal S and Kumar, R Pravin and Ramachandra, Nallur B and Sparrow, John C and Nongthomba, R Pravin (2012) Mutations in Drosophila Myosin Rod Cause Defects in Myofibril Assembly. In: JOURNAL OF MOLECULAR BIOLOGY, 419 (1-2). pp. 22-40.
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The roles of myosin during muscle contraction are well studied, but how different domains of this protein are involved in myofibril assembly in vivo is far less understood. The indirect flight muscles (IFMs) of Drosophila melanogaster provide a good model for understanding muscle development and function in vivo. We show that two missense mutations in the rod region of the myosin heavy-chain gene, Mhc, give rise to IFM defects and abnormal myofibrils. These defects likely result from thick filament abnormalities that manifest during early sarcomere development or later by hypercontraction. The thick filament defects are accompanied by marked reduction in accumulation of flightin, a myosin binding protein, and its phosphorylated forms, which are required to stabilise thick filaments. We investigated with purified rod fragments whether the mutations affect the coiled-coil structure, rod aggregate size or rod stability. No significant changes in these parameters were detected, except for rod thermodynamic stability in one mutation. Molecular dynamics simulations suggest that these mutations may produce localised rod instabilities. We conclude that the aberrant myofibrils are a result of thick filament defects, but that these in vivo effects cannot be detected in vitro using the biophysical techniques employed. The in vivo investigation of these mutant phenotypes in IFM development and function provides a useful platform for studying myosin rod and thick filament formation generically, with application to the aetiology of human myosin rod myopathies. (C) 2012 Elsevier Ltd. All rights reserved.
|Item Type:||Journal Article|
|Additional Information:||Copyright for this article belongs to Elsevier B V|
|Keywords:||INDIRECT FLIGHT MUSCLES;HELICAL COILED-COILS;HEAVY-CHAIN GENE;PARAMYOSIN MINIPARAMYOSIN GENE;MOLECULAR-DYNAMICS SIMULATIONS;STRETCH-ACTIVATED MUSCLES;INSECT FLIGHT; CAENORHABDITIS-ELEGANS;TROPONIN-I;PROTEIN STRUCTURES|
|Department/Centre:||Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)|
|Date Deposited:||18 Jul 2012 04:48|
|Last Modified:||18 Jul 2012 04:49|
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