PRIMARY STRUCTURE AND MUSCLE-SPECIFIC EXPRESSION OF THE 50-KDA DYSTROPHIN-ASSOCIATED GLYCOPROTEIN (ADHALIN)

The 50-kDa dystrophin-associated glycoprotein (50-DAG) is a component of the dystrophin-glycoprotein complex, which links the muscle cytoske leton to the extracellular matrix. 50-DAG is specifically deficient in skeletal muscle of patients with severe childhood autosomal recessive muscular dystrophy and in skeletal and cardiac muscles of BIO 14.6 ca rdiomyopathic hamsters. The lack of 50-DAG leads to a disruption and d ysfunction of the dystrophin-glycoprotein complex in these diseases. T he cDNA encoding 50-DAG has now been cloned from rabbit skeletal muscl e. The 50-DAG deduced amino acid sequence predicts a novel protein hav ing 387 amino acids, a 17-amino acid signal sequence, one transmembran e domain, and two potential sites of N-linked glycosylation. Affinity- purified antibodies against rabbit 50-DAG fusion proteins or synthetic peptides specifically recognized a 50-kDa protein in skeletal muscle sarcolemma and the 50-kDa component of the dystrophin-glycoprotein com plex. In contrast to dystroglycan, which is expressed in a wide variet y of muscle and non-muscle tissues, 50-DAG is expressed only in skelet al and cardiac muscles and in selected smooth muscles. Finally, 50-DAG mRNA is present in mdx and Duchenne muscular dystrophy (DMD) muscle, indicating that the down-regulation of this protein in DMD and the mdx mouse is likely a post-translational event.