title: Differential heparin sensitivity of alpha-dystroglycan binding to laminins expressed in normal and dy/dy mouse skeletal muscle.
abstract: The alpha-dystroglycan binding properties of laminins extracted from fully differentiated skeletal muscle were characterized. We observed that the laminins expressed predominantly in normal adult rat or mouse skeletal muscle bound alpha-dystroglycan in a Ca2+-dependent, ionic strength-sensitive, but heparin-insensitive manner as we had observed previously with purified placental merosin (Pall, E. A., Bolton, K. M., and Ervasti, J. M. 1996 J. Biol. Chem. 271, 3817-3821). Rat skeletal muscle laminins partially purified by heparin-agarose affinity chromatography also bound alpha-dystroglycan without sensitivity to heparin. We also confirm previous studies of dystrophic dy/dy mouse skeletal muscle showing that the alpha2 chain of merosin is reduced markedly and that the laminin alpha1 chain is not up-regulated detectably. However, we further observed a quantitative decrease in the expression of laminin beta/gamma chain immunoreactivity in alpha2 chain-deficient dy/dy skeletal muscle and reduced alpha-dystroglycan binding activity in laminin extracts from dy/dy muscle. Most interestingly, the alpha-dystroglycan binding activity of residual laminins expressed in merosin-deficient dy/dy skeletal muscle was inhibited dramatically (69 +/- 19%) by heparin. These results identify a potentially important biochemical difference between the laminins expressed in normal and dy/dy skeletal muscle which may provide a molecular basis for the inability of other laminin variants to compensate fully for the deficiency of merosin in some forms of muscular dystrophy.
authors.affiliation: Graduate Program in Molecular and Cellular Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: McDearmon
authors.forename: A L
authors.initials: AL
authors.lastname: Burwell
authors.forename: A C
authors.initials: AC
authors.lastname: Combs
authors.forename: B A
authors.initials: BA
authors.lastname: Renley
authors.forename: M T
authors.initials: MT
authors.lastname: Sdano
authors.forename: J M
authors.initials: JM
authors.lastname: Ervasti
mesh_terms: D000818:Animals; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism*; D049030:Dystroglycans; D005260:Female; D005786:Gene Expression Regulation; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D007797:Laminin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017474:Receptors, Laminin / Q000378:metabolism; D012016:Reference Values
chemical_list: D003598:Cytoskeletal Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D017474:Receptors, Laminin; D049030:Dystroglycans; D006493:Heparin