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Hemin inhibits internalization of transferrin by reticulocytes and promotes phosphorylation of the membrane transferrin receptor.

By T M Cox, M W O'Donnell, P Aisen and I M London


Addition of hemin to reticulocytes inhibits incorporation of iron from transferrin [Ponka, P. & Neuwirt, J. (1969) Blood 33, 609-707]. Heme also regulates protein synthesis in immature erythroid cells through its effects on phosphorylation of the initiation factor eIF-2. We have therefore examined its effects on endocytosis of iron-transferrin and phosphorylation of the transferrin receptor. Hemin (10-50 microM) reduced iron transport but increased cell-associated transferrin. When intracellular iron delivery was inhibited by NH4Cl, no such increase in cell-associated transferrin was seen. During uptake of 125I-labeled transferrin in the steady state, the use of a washing technique to dissociate bound transferrin on the cell membrane showed that radioligand accumulated on the surface of hemin-treated cells. Hemin reduced the initial influx of transferrin, thereby diminishing incorporation of iron. Receptor phosphorylation was investigated by immunoprecipitation of reticulocyte extracts after metabolic labeling with [32P]Pi. In the absence of ligand, phosphorylated receptor was chiefly localized on cell stroma. Exposure to transferrin increased cytosolic phosphorylated receptor from 15-30% to approximately 50% of the total, an effect overcome by hemin treatment. Addition of hemin in the presence of transferrin enhanced net phosphorylated receptor in the reticulocyte in association with a redistribution of phosphorylated receptor to stromal membranes. The findings suggest a possible relationship of phosphorylation to endocytosis of the transferrin receptor in reticulocytes

Topics: Research Article
Year: 1985
DOI identifier: 10.1073/pnas.82.15.5170
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Provided by: PubMed Central
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