SKELEMIN, A CYTOSKELETAL M-DISC PERIPHERY PROTEIN, CONTAINS MOTIFS OFADHESION RECOGNITION AND INTERMEDIATE FILAMENT PROTEINS

In striated muscle, myofibrils are anchored to an interconnecting cyto skeleton of desmin intermediate filaments. Skelemin (195 kDa) may be a link between myofibrils and the intermediate filament cytoskeleton. S kelemin partitions with desmin to the insoluble cytoskeleton, and incr eases the thickness of reconstituted intermediate filaments. Concentra ted at the M-disc periphery, skelemin may also contact myosin filament s. We used immunoscreening to isolate a mouse muscle cDNA which encode s a protein with a calculated molecular mass of 185 kDa. Anti-skelemin antibodies bound to the protein products of each of three nonoverlapp ing regions of the open reading frame. Antibodies directed against the protein products of each one-third of the cDNA react with a 195-kDa m uscle protein and stain the M-disc indistinguishably from the original anti-skelemin antibodies, suggesting that the cDNA encodes skelemin. A single skelemin mRNA is detected in muscle but not non-muscle tissue s, consistent with immunostaining results. Skelemin is a member of a f amily of myosin-associated proteins containing fibronectin type III an d immunoglobulin superfamily C2 motifs. Skelemin is unique in this fam ily in having intermediate filament core-like motifs, one near each te rminus. We hypothesize that skelemin could interact with myosin or myo sin-associated proteins through its fibronectin and/or immunoglobulin motifs, and with intermediate filaments through intermediate filament- like motifs.