Analysis of pathogenesis induced by defects of intermediate filament networks.

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Our ultrastructural and biochemical analyses revealed that plectin molecules tethered intermediate filaments onto subsarcolemmal dense plaques containing dystrophin complexes. Further more precise analyses of molecular interaction disclosed that plectin bound desmuslin, which, in turn, interacted with dystrobrevin associated with dystrophins beneath the sarcolemma. In addition to interlinking role of desmuslin, desmuslin appeared to copolymerize with desmin, forming heteropolymerized intermediate filaments. Based on these findings, we studied the phenotypic changes of intermediate filament networks in mdx mice lacking dystrophin. Despite of the absence of dystrophin, dystrobrevin was still found under the sarcolemma, probably due to up regulated expression of urtophin as substitutive protein. Increased immunoreactivities of plectin and desmuslin were identified in the subsarcolemmal space of intact fibers as well as regenerating fibers with central nuclei. This accumulation of intermediate filaments proteins under the sarcolemma of mdx mice suggest desmuslin and plectin may participate in the pathogenesis of muscular dystrophy.