Interactions of ricin with sinusoidal endothelial rat liver cells. Different involvement of two distinct carbohydrate-specific mechanisms in surface binding and internalization.
We have investigated the interactions of the plant toxin ricin with sinusoidal endothelial rat liver cells (EC). In these cells, ricin can be bound and internalized via either cell surface galactosyl residues or mannose receptors. Binding and uptake via galactosyl residues and mannose receptors was studied in the presence of mannan (1 mg/ml) and lactose (50 mM) respectively. Whereas most of the ricin binding was accounted for by cell surface galactosyl residues, uptake of ricin via mannose receptors was much more efficient than uptake via galactosyl residues. Internalized ricin is subject to extensive retroendocytosis (recycling to the cell surface from an early endocytic compartment). Retroendocytosis occurs after internalization of ricin via either pathway and to a much greater extent than for other glycoproteins taken up via mannose receptors of the EC. Hyperosmolarity (150 mM-sucrose), which is known to inhibit endocytosis from coated pits, strongly inhibited ricin uptake via mannose receptors, but had less effect on uptake via galactosyl residues. This suggests that only part of the galactose-specific uptake takes place from coated pits. Protein synthesis in EC was very sensitive to ricin [concn. causing half-maximal inhibition (IC50) = 1.3 x 10(-13) M]. Mannan was slightly more effective than lactose in protecting the EC protein synthesis from ricin toxicity.
Magnusson
S
S
Department of Biology, University of Oslo, Norway.
Berg
T
T
Turpin
E
E
Frénoy
J P
JP
D000818:Animals; D001692:Biological Transport; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004705:Endocytosis; D004727:Endothelium / Q000378:metabolism*; D005697:Galactosides / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D012276:Ricin / Q000378:metabolism*
D005697:Galactosides; D012276:Ricin