Investigations into the pathobiology of thin-filament myopathies.

摘要: Mutations in actin and tropomyosin, identified patients with myopathic disease have been used tissue culture models functional studies a view to understand how these mutations impact on skeletal muscle structure function result weakness. The likely mode of pathogenesis disorders is via dominant negative effect i.e., the production ‘poison’ proteins that interfere normal native protein. Tissue vitro binding highlight defects different mutants including abnormal folding, aggregation altered polymerization which would function. most widely studied mutation tropomyosin M9R substitution large Australian family nemaline myopathy. mutant protein has reduced affinity for actin, does not bind tropomodulin model peptide results sensitivity isometric force activating calcium cardiac myocytes. pathological consequences troponin, nebulin, cofilin are also discussed. Although α-actinin associated NM, using tagged constructs regions gene suggest this plays role body formation.