Effects of monensin on the receptor-mediated endocytosis of 125I-labelled IgG by guinea-pig yolk sac in vitro.
The effects of the carboxylic ionophore, monensin, on the receptor-mediated binding and uptake of 125I-labelled IgG by the guinea-pig yolk sac have been studied in vitro. Exposure of tissue to 10 microM monensin resulted in a rapid inhibition of uptake which correlated with a time- and temperature-dependent loss of cell-surface receptor activity. Monensin appeared to bring about a change in receptor distribution since the lost activity could be detected after permeabilizing the tissue with saponin. Electron microscopic examination of monensin-treated tissue revealed that the apical plasma membrane of endoderm cells was depleted of coated and uncoated pits and that the apical cytoplasm contained numerous large vacuoles. Dilation of the Golgi apparatus was also observed. Normal surface receptor activity and ultrastructural features could be largely recovered by removal of monensin. Recovery of receptor activity was unaffected by the presence of cycloheximide. These results are consistent with a model in which IgG receptors are recycled and in which monensin blocks this process by causing receptors to be trapped intracellularly. Ammonium chloride or a combination of valinomycin and carbonyl cyanide p-(trifluoromethoxy)-phenylhydrazone also brought about a loss of surface IgG receptors, lending support to the idea that inhibition of recycling was the result of perturbation of an intracellular acidification event and implying that passage through an acidic compartment may be important for correct receptor processing.
Douglas
G C
GC
Department of Human Anatomy, School of Medicine, University of California, Davis 95616.
King
B F
BF
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008985:Monensin / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D015017:Yolk Sac / Q000187:drug effects / Q000648:ultrastructure*
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D017452:Receptors, IgG; D008985:Monensin