title: Disruption of perlecan binding and matrix assembly by post-translational or genetic disruption of dystroglycan function.
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.
authors.affiliation: Department of Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 400 Eckstein Medical Building, Iowa City, IA 52242, USA.
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Michele
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Satz
authors.forename: Rita
authors.initials: R
authors.lastname: Barresi
authors.forename: Hajime
authors.initials: H
authors.lastname: Kusano
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Rupert
authors.initials: R
authors.lastname: Timpl
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006031:Glycosylation; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational
chemical_list: D000911:Antibodies, Monoclonal; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; C071927:perlecan; D049030:Dystroglycans; C117674:LARGE1 protein, human; D017351:N-Acetylglucosaminyltransferases