Internalization and recycling of transferrin and its receptor. Effect of trifluoperazine on recycling in human erythroleukemic cells.
When human erythroleukemic (K562) cells were incubated with 25 microM trifluoperazine (TFP), a drug that inhibits both calmodulin-dependent and calcium-activated phospholipid-dependent kinases, the number of transferrin receptors detected on the cell surface was reduced to approximately half with no change in the affinity of the remaining surface receptors. Removal of the TFP from the incubation medium reversed the loss of surface receptors and they returned to the cell surface in an apparently synchronous manner. As a result, the number of receptors detected on the cell surface exceeded the original level but later returned to normal. Measurements of the total number of receptors available to transferrin in TFP-treated cells suggested that the lost receptors were not participating in the internalization and recycling pathway but instead were probably trapped at an intracellular location. However, those receptors that remained on the cell surface continued to internalize transferrin and to recycle apotransferrin to the cell surface albeit more slowly than in cells that had not been treated with TFP. Using transferrin that had been labeled with iron-59, it was found that although iron uptake was reduced in line with the diminished number of surface receptors, iron still accumulated within TFP-treated cells, suggesting that in the presence of the drug, transferrin-transferrin receptor complexes continued to migrate through an intracellular compartment that contained a low pH.
D002478:Cells, Cultured; D006801:Humans; D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin; D013696:Temperature; D014168:Transferrin / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D014268:Trifluoperazine