Membrane glycoprotein receptor and hole-forming properties of a cytolytic protein toxin.
Aerolysin, a cytolytic bacterial exotoxin, was radioiodinated by using the Iodogen reagent. Binding of the labeled toxin to rat erythrocytes was inhibited by the native protein and by anti-aerolysin antibody. Toxin, once bound, was not removed by the addition of a large excess of free aerolysin. Binding of the radioactive toxin to erythrocytes of different species paralleled the hemolytic specificity of the unlabeled toxin. Pretreatment of the rat erythrocytes with trypsin, which removed a major membrane glycoprotein, resulted in a dramatic decrease in binding, whereas chymotrypsin treatment had no effect. Binding was inhibited by a glycoprotein fraction isolated from these cells but not by a total rat erythrocyte glycolipid preparation. Aerolysin caused the formation of holes in erythrocytes which were sized by measuring the release of labeled molecular weight markers. Glucagon (molecular weight 3550) and smaller molecules entrapped in human or rat erythrocytes were released by treatment with aerolysin, whereas methoxyinulin (molecular weight 5500) and larger molecules were not. Aerolysin also caused the release of glucose from large unilamellar lipid vesicles. The results indicate that a specific glycoprotein receptor facilitates the interaction of aerolysin with erythrocyte membranes. Binding is followed by the formation of discrete holes or pores, and this results in cell rupture by a colloid-osmotic process.
D000333:Aeromonas / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008970:Molecular Weight; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism
D001427:Bacterial Toxins; D003603:Cytotoxins; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D052899:Pore Forming Cytotoxic Proteins; D011955:Receptors, Drug; C032676:aerolysin; D005934:Glucagon