Biosynthesis of dystroglycan: processing of a precursor propeptide

Dystroglycan is a cytoskeleton-linked extracellular matrix receptor express ed in many cell types. Dystroglycan is composed of alpha- and beta-subunits which are encoded by a single mRNA. Using a heterologous mammalian express ion system, we provide the first biochemical evidence of the alpha/beta-dys troglycan precursor propeptide prior to enzymatic cleavage. This 160 kDa dy stroglycan propeptide is processed into alpha- and beta-dystroglycan (120 k Da and 43 kDa, respectively), We also demonstrate that the precursor propep tide is glycosylated and that blockade of asparagine-linked (N-linked) glyc osylation did not prevent the cleavage of the dystroglycan precursor peptid e. However, inhibition of N-linked glycosylation results in aberrant traffi cking of the alpha- and beta-dystroglycan subunits to the plasma membrane. Thus, dystroglycan is synthesized as a precursor propeptide that is post-tr anslationally cleaved and differentially glycosylated to yield alpha- and b eta-dystroglycan. (C) 2000 Federation of European Biochemical Societies.