ABSTRACT

The cytoskeletal protein dystrophin, the protein product of the Duchenne muscular dystrophy gene, is associated with a number of cell membrane glycoproteins, including α- and β-dystroglycans which are encoded a single gene and cleaved by posttranslational processing. α-dystroglycan is an extracellular mucin-type glycoprotein and anchored to the extracellular domain of the transmembrane glycoprotein β- dystroglycan. α-dystroglycan binds laminin in the basement membrane, while β-dystroglycan is anchored to dystrophin and its homologues in the cytoplasm. Thus, the dystroglycan complex, comprised of α- and β-dystroglycans, spans the cell membrane and links the basement membrane with the intracellular cytoskeleton. The dystroglycan complex is expressed ubiquitously in various tissues and plays an important role in the assembly and maintenance of the basement membrane. While the null mutation of the dystroglycan gene causes premature death of the embryos because of disruption of the extra-embryonic basement membrane, recent studies have implicated dysfunction of the dystroglycan complex in a wide variety of pathological conditions, including viral infections, nephritic syndrome, cancer invasion and metastasis. In the field of neuromuscular diseases, dysfunction of the dystroglycan complex has been implicated in the molecular pathogenesis of not only congenital and limb-girdle muscular dystrophies but also hereditary demyelinating neuropathies. In addition, Mycobacterium leprae, the causative agent of leprosy, has been shown to use the dystroglycan complex as the receptor to infect Schwann cells. All together, these findings point to the crucial role of the dystroglycan complex in the viability and function of various cells and tissues.