title: Gangliosides indirectly inhibit the binding of laminin to sulfatides.
abstract: Laminin, a glycoprotein of basement membranes, agglutinates aldehyde-fixed erythrocytes. Laminin-mediated hemagglutination is strongly inhibited by some gangliosides and anionic phospholipids. Laminin, however, binds only to sulfatides among the lipids extracted from erythrocytes. We now report that gangliosides are remarkably potent inhibitors of laminin binding to sulfatides when both lipids are adsorbed on plastic. A 50% inhibition of laminin binding to 100 ng of sulfatides is obtained with 10 ng of GM3 and 8 ng of GM1, respectively. Mixing of sulfatides with neutral glycolipids, phosphatidyl choline, or cholesterol does not inhibit laminin binding, whereas mixing with sulfatide-depleted erythrocyte lipids enhances binding. Inhibition of binding by gangliosides is not due to competition for adsorption to the plastic, as preincubation of the adsorbed lipids with neuraminidase reverses inhibition by GM3, but not by GM1 which is not a substrate for the enzyme. These results are consistent with the observations that treatment of fixed erythrocytes with neuraminidase increases their agglutinability by laminin and that pretreatment of erythrocytes with gangliosides followed by washing gives similar inhibition as seen when gangliosides are present as competitive inhibitors. Thus, inhibition of laminin-mediated agglutination by gangliosides probably results from masking of erythrocyte sulfatides due to adsorption of gangliosides onto the membrane rather than from a direct competition for laminin binding sites.
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D005732:Gangliosides / Q000378:metabolism / Q000494:pharmacology*; D006386:Hemagglutination Tests; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D007797:Laminin; D008563:Membrane Lipids; D013433:Sulfoglycosphingolipids