Biosynthesis of dystroglycan: processing of a precursor propeptide

AbstractDystroglycan is a cytoskeleton-linked extracellular matrix receptor expressed in many cell types. Dystroglycan is composed of α- and β-subunits which are encoded by a single mRNA. Using a heterologous mammalian expression system, we provide the first biochemical evidence of the α/β-dystroglycan precursor propeptide prior to enzymatic cleavage. This 160 kDa dystroglycan propeptide is processed into α- and β-dystroglycan (120 kDa and 43 kDa, respectively). We also demonstrate that the precursor propeptide is glycosylated and that blockade of asparagine-linked (N-linked) glycosylation did not prevent the cleavage of the dystroglycan precursor peptide. However, inhibition of N-linked glycosylation results in aberrant trafficking of the α- and β-dystroglycan subunits to the plasma membrane. Thus, dystroglycan is synthesized as a precursor propeptide that is post-translationally cleaved and differentially glycosylated to yield α- and β-dystroglycan