Binding and Uptake of the Toxic Lectin Modeccin by Baby Hamster Kidney (BHK) Cells. Isolation of Mutants Defective in the Internalization of Modeccin

The effects of the toxic lectins, ricin and modeccin, on baby hamster kidney (BHK) cells have been compared. Modeccin is about 20-50 times more toxic to BHK cells than ricin. Binding studies showed that there are 10(5) to 2 X 10(5) modeccin binding sites/cell compared with approximately 10(7) binding sites for ricin. Inhibition studies with galactosides indicate that both N- and O-glycans with terminal galactosyl residues are effective inhibitors of modeccin binding. Surface-bound modeccin, at 0 degrees C, was found to be very rapidly endocytosed (75-80% in 10 min) when cells were warmed to 37 degrees C. Two modeccin-resistant BHK cell lines have been isolated and characterized. These mutants bind normal levels of modeccin and retain sensitivity to the toxic action of ricin. Both cell lines were shown to be defective in their ability to internalize modeccin. Also, these mutants are morphologically different from parental cells as they align and elongate very prominently at low cell densities. These mutants will be very useful in understanding the mechanism of uptake and transport of modeccin.