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- W2149421605 abstract "Desmin intermediate filaments intimately surround myofibrils in vertebrate muscle forming a mesh-like filament network. Desmin attaches to sarcomeres through its high-affinity association with nebulin, a giant F-actin binding protein that co-extends along the length of actin thin filaments. Here, we further investigated the functional significance of the association of desmin and nebulin in cultured primary myocytes to address the hypothesis that this association is key in integrating myofibrils to the intermediate filament network. Surprisingly, we identified eight peptides along the length of desmin that are capable of binding to C-terminal modules 160–170 in nebulin. In this study, we identified a targeted mutation (K190A) in the desmin coil 1B region that results in its reduced binding with the nebulin C-terminal modules. Using immunofluorescence microscopy and quantitative analysis, we demonstrate that expression of the mutant desmin K190A in primary myocytes results in a significant reduction in assembled endogenous nebulin and desmin at the Z-disc. Non-uniform actin filaments were markedly prevalent in myocytes expressing GFP-tagged desmin K190A, suggesting that the near-crystalline organization of actin filaments in striated muscle depends on a stable interaction between desmin and nebulin. All together, these data are consistent with a model in which Z-disc-associated nebulin interacts with desmin through multiple sites to provide efficient stability to satisfy the dynamic contractile activity of myocytes." @default.
- W2149421605 created "2016-06-24" @default.
- W2149421605 creator A5011589990 @default.
- W2149421605 creator A5046990808 @default.
- W2149421605 date "2011-10-15" @default.
- W2149421605 modified "2023-10-04" @default.
- W2149421605 title "The desmin coil 1B mutation K190A impairs nebulin Z-disc assembly and destabilizes actin thin filaments" @default.
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- W2149421605 doi "https://doi.org/10.1242/jcs.087080" @default.
- W2149421605 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3196858" @default.
- W2149421605 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21984811" @default.
- W2149421605 hasPublicationYear "2011" @default.
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