Disruption of perlecan binding and matrix assembly by post-translational or genetic disruption of dystroglycan function.
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.
Kanagawa
Motoi
M
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.
Michele
Daniel E
DE
Satz
Jakob S
JS
Barresi
Rita
R
Kusano
Hajime
H
Sasaki
Takako
T
Timpl
Rupert
R
Henry
Michael D
MD
Campbell
Kevin P
KP
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
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