Biosynthesis of dystroglycan: processing of a precursor propeptide

FEBS Lett. 2000 Feb 18;468(1):79-83. doi: 10.1016/s0014-5793(00)01195-9.

Abstract

Dystroglycan is a cytoskeleton-linked extracellular matrix receptor expressed in many cell types. Dystroglycan is composed of alpha- and beta-subunits which are encoded by a single mRNA. Using a heterologous mammalian expression system, we provide the first biochemical evidence of the alpha/beta-dystroglycan precursor propeptide prior to enzymatic cleavage. This 160 kDa dystroglycan propeptide is processed into alpha- and beta-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 alpha- and beta-dystroglycan subunits to the plasma membrane. Thus, dystroglycan is synthesized as a precursor propeptide that is post-translationally cleaved and differentially glycosylated to yield alpha- and beta-dystroglycan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidohydrolases / metabolism
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cell Membrane / metabolism
  • Cricetinae
  • Culture Media, Conditioned / metabolism
  • Cytomegalovirus / genetics
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / genetics
  • Dystroglycans
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Vectors
  • Glycosylation
  • Immunoblotting
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Molecular Sequence Data
  • Molecular Weight
  • Oligosaccharides / metabolism
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Peptides / metabolism*
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational*
  • RNA, Messenger / metabolism
  • Rabbits
  • Transfection
  • Tunicamycin / metabolism

Substances

  • Culture Media, Conditioned
  • Cytoskeletal Proteins
  • Membrane Glycoproteins
  • Oligosaccharides
  • Peptides
  • Protein Precursors
  • RNA, Messenger
  • Tunicamycin
  • Dystroglycans
  • Amidohydrolases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase