Desmuslin, an intermediate filament protein that interacts with alpha-dystrobrevin and desmin

Dystrobrevin is a component of the dystrophin-associated protein complex an d has been shown to interact directly with dystrophin, alpha1-syntrophin, a nd the sarcoglycan complex. The precise role of alpha -dystrobrevin in skel etal muscle has not yet been determined. To study alpha -dystrobrevin's fun ction in skeletal muscle, we used the yeast two-hybrid approach to look for interacting proteins. Three overlapping clones were identified that encode d an intermediate filament protein we subsequently named desmuslin (DMN). S equence analysis revealed that DMN has a short N-terminal domain, a conserv ed rod domain, and a long C-terminal domain, all common features of type 6 intermediate filament proteins. A positive interaction between DMN and a-dy strobrevin was confirmed with an in vitro coimmunoprecipitation assay. By N orthern blot analysis, we find that DMN is expressed mainly in heart and sk eletal muscle, although there is some expression in brain. Western blotting detected a 160-kDa protein in heart and skeletal muscle. Immunofluorescent microscopy localizes DMN in a stripe-like pattern in longitudinal sections and in a mosaic pattern in cross sections of skeletal muscle. Electron mic roscopic analysis shows DMN colocalized with desmin at the Z-lines. Subsequ ent coimmunoprecipitation experiments confirmed an interaction with desmin. Our findings suggest that DMN may serve as a direct linkage between the ex tracellular matrix and the Z-discs (through plectin) and may play an import ant role in maintaining muscle cell integrity.