Phenotypic reversion of ricin-resistant hamster fibroblasts to a sensitive state after coating with glycolipid receptors

Abstract

THE cytotoxicity of the plant lectin ricin, of Ricinus communis seeds, towards mammalian cells is mediated in three steps¹. Binding of the toxin to cell surface galactose or N-acetylgalactosamine receptors is followed by entry of the bound lectin into the cells, perhaps by endocytosis^2,3 and inhibition of protein synthesis^4–6. Several variant lines of cells selected for resistance to ricin have been shown^7–10 to bind ricin poorly and to carry much smaller amounts of receptors at the cell surface. We report here that when such a resistant cell line of baby hamster kidney (BHK) fibroblasts^8,9 is incubated with a ricin-binding glycolipid fraction prepared from human erythrocytes, glycolipid is taken up and the cells exhibit increased binding of ricin and greater sensitivity to lectin-mediated inhibition of cell protein synthesis. These studies suggest that glycolipids can function in certain circumstances as membrane receptors in the binding of ricin and mediation of ricin cytotoxicity.