Subcellular fractionation of dystrophin to the triads of skeletal muscle.

Duchenne muscular dystrophy (DMD) is a human X-linked biochemical defect resulting in the progressive wasting of skeletal muscle of affected individuals. It is the most common and is considered to be the most devastating of the muscular dystrophies, affecting about 1 in 3,500 live-born males. The gene that, when defective, results in this disorder was recently isolated. Using the cloned complementary DNA sequences corresponding to the DMD gene, antibodies have been produced that react with a protein species of relative molecular mass (Mr) approximately 400,000 (400K) which was absent in two DMD-affected individuals and in mdx mice. This protein species is called dystrophin because of its identification by molecular-genetic analysis of affected individuals. Here we show that dystrophin is associated with the triadic junctions in skeletal muscle, and is therefore probably involved with Ca2+ homoeostasis. We also show that the approximately 450K ryanodine receptor/sarcoplasmic reticulum Ca2+ channel, which has the large size and subcellular distribution characteristics of dystrophin, is an immunologically distinct protein species.