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Biosynthesis of dystroglycan: processing of a precursor propeptide
Author(s) -
Holt Kathleen H.,
Crosbie Rachelle H.,
Venzke David P.,
Campbell Kevin P.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01195-9
Subject(s) - dystroglycan , protein precursor , glycosylation , chemistry , biochemistry , microbiology and biotechnology , biology , extracellular matrix , laminin , gene
Dystroglycan 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.