Disruption of perlecan binding and matrix assembly by post-translational or genetic disruption of dystroglycan function

FEBS Lett. 2005 Aug 29;579(21):4792-6. doi: 10.1016/j.febslet.2005.07.059.

Abstract

Dystroglycan is a cell-surface matrix receptor that requires LARGE-dependent glycosylation for laminin binding. Although the interaction of dystroglycan with laminin has been well characterized, less is known about the role of dystroglycan glycosylation in the binding and assembly of perlecan. We report reduced perlecan-binding activity and mislocalization of perlecan in the LARGE-deficient Large(myd) mouse. Cell-surface ligand clustering assays show that laminin polymerization promotes perlecan assembly. Solid-phase binding assays provide evidence for the first time of a trimolecular complex formation of dystroglycan, laminin and perlecan. These data suggest functional disruption of the trimolecular complex in glycosylation-deficient muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Dystroglycans* / genetics
  • Dystroglycans* / metabolism
  • Extracellular Matrix / metabolism*
  • Glycosylation
  • Heparan Sulfate Proteoglycans / metabolism*
  • Humans
  • Laminin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiprotein Complexes
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational

Substances

  • Antibodies, Monoclonal
  • Heparan Sulfate Proteoglycans
  • Laminin
  • Multiprotein Complexes
  • Neoplasm Proteins
  • perlecan
  • Dystroglycans
  • LARGE1 protein, human
  • N-Acetylglucosaminyltransferases