Functional Flexibility of Dystroglycan, a Transmembrane Linker Between the Extracellular Matrix and the Cytoskeleton.

Dystroglycan, originally identified in muscle as a component of the dystrophin-associated glycoprotein complex (DGC), is a ubiquitously expressed cell-surface receptor that forms a transmembrane link between the extracellular matrix and the cytoskeleton. Dystroglycan contains two subunits, α and β, formed by proteolytic cleavage of a common precursor. Disruption of the dystrophin-dystroglycan complex in several forms of dystrophy suggests that extracellular matrix-cytoskeleton linkage is important in maintaining the structural integrity of the sarcolemma and muscle cell viability. Dystroglycan is expressed in a variety of cell types from early development into adulthood, indicating that its function is not restricted to muscle. Recently α-dystroglycan has been found to be the common receptor for viral and bacterial agents of disease. The binding partners of dystroglycan in different cell types and in specialized regions of a single cell type may differ. The cytoplasmic tail of β-dystroglycan binds proteins involved in signal transduction and cytoskeleton organization, or in clustering neurotransmitter receptors. Cognitive impairment is often associated with muscular defect in patients affected by Duchenne (DMD) and Becker muscular dystrophy. The brain dysfunction in DMD is recognized to be a non-progressive disorder that occurs early, probably during embryogenesis. Although the molecular organization of the DGC in brain is currently unknown, the expression and assembly of the DGC components during development may be important in establishing the DMD-associated neuronal. Dystroglycan is expressed in neuronal subtypes of specific brain areas involved in learning and memory processes, and in glial cells at the blood-brain barrier and in contact with the basal membrane. Dystroglycan immunoreactivity was preferentially associated with the postsynaptic specializations and with the endfeet of astrocytes around blood vessels; thus suggesting that dystroglycan may participate in the organization of highly specialized intercellular contacts by maintaining the integrity of the extracellular matrix-cytoskeleton linkage.