[Dystrophin, dystrophin-associated protein and dystrophinopathy]

Dystrophin is a protein product of the gene responsible for Duchenne muscular dystrophy (DMD), and is a long slender protein localized at the protoplasmic surface of sarcolemma. Dystrophin binds with actin filaments at its amino-terminal region, and with dystrophin-associated proteins (DAPs) at its carboxyl-terminal region. DAPs are composed of a glycoprotein complex and a syntrophin complex, a complex of proteins binding with dystrophin and located intracellularly. Glycoprotein complex is composed of dystroglycan complex and sarcoglycan complex, both of which are membrane-integrated. Dystrophin binds with dystroglycan complex which transverse through sarcolemma and then binds with laminin in the basal lamina, forming a long axis between action threads and the extracellular matrix. Sarcoglycan complex does not directly bind with dystrophin but binds with dystroglycan complex. Disruption of the axis results in dystrophic changes in one kind of congenital muscular dystrophy (CMD). Loss of the sarcoglycan complex gives rise to childhood severe autosomal recessive muscular dystrophy (SCARMD) which is clinically very similar to DMD. In DMD, the sarcoglycan complex is mostly lost, and the axis is for the most part defective. Therefore, it is likely that the causes of DMD and SCARMD may be similar and may be modified by the mechanism which gives rise to CMD.