Trichosanthin interacts with and enters cells via LDL receptor family members

The type-I ribosome-inactivating protein trichosan-thin displays selective cytotoxicity, suggesting specific mechanisms for entry into cells, Here we show that trichosanthin binds specifically to the endocytic receptors LRP a nd megalin, and that binding as well as uptake into cells is inhibited by t he receptor-associated protein (RAP). The results suggest that the known ab ortifacient and renotoxic actions of trichosanthin are caused by LRP-mediat ed uptake in trophoblasts and megalin-mediated uptake in proximal tubule ep ithelial cells, respectively, (C) 2000 Academic Press.