Ganglioside inhibition of fibronectin-mediated cell adhesion to collagen.
Fibronectin mediates the adhesion of cells to collagen by first binding to the collagen substrate, followed by attachment of the cells to the fibronectin-collagen complex. Bovine brain gangliosides were found to block fibronectin-mediated cell adhesion to collagen in a concentration-dependent manner. The gangliosides did not block the binding of fibronectin to collagen but did prevent the attachment of the cells to the fibronectin-collagen complex. Of the individual gangliosides tested, GT1 and GD1a were the most effective inhibitors followed by GD1b greater than GM1 greater than GM2; GM3 was not an inhibitor. The inhibition of cell adhesion also was observed with the oligosaccharide portion of the gangliosides, but not with ceramides or with a variety of free sugars or glycosaminoglycans. Mild periodate oxidation of mixed gangliosides or of GD1a modified their sialic acid residues and the oxidized gangliosides were no longer inhibitory; subsequent reduction with NaBH4 did not restore the inhibitory activity of the modified gangliosides. These results suggest that specific gangliosides or related sialic acid-containing glycoconjugates on the cell surface may act as the receptors for fibronectin.
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D005260:Female; D005353:Fibronectins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology*; D009439:Neuraminidase / Q000494:pharmacology; D010053:Ovary
D005353:Fibronectins; D005732:Gangliosides; D003094:Collagen; D009439:Neuraminidase