Demonstration of two distinct transferrin receptor recycling pathways and transferrin-independent receptor internalization in K562 cells.
The endocytosis and recycling of the human transferrin receptor were evaluated by several experimental modalities in K562 cells perturbed with 10(-5) M monensin. The work presented is an extension of a previous study demonstrating both complete inhibition of release of internalized human transferrin and a 50% reduction in the number of cell surface transferrin binding sites in K562 cells treated with monensin (Stein, B. S., Bensch, K. G., and Sussman, H. H. (1984) J. Biol. Chem. 259, 14762-14772). The data directly reveal the existence of two distinct transferrin receptor recycling pathways. One pathway is monensin-sensitive and is felt to represent recycling of transferrin receptors through the Golgi apparatus, and the other pathway is monensin-resistant and most likely represents non-Golgi-mediated transferrin receptor recycling. A transferrin-free K562 cell culture system was developed and used to demonstrate that cell surface transferrin receptors can be endocytosed without antecedent ligand binding, indicating that there are factors other than transferrin binding which regulate receptor internalization. Evidence is presented suggesting that two transferrin receptor recycling pathways are also operant in K562 cells under ligand-free conditions, signifying that trafficking of receptor into either recycling pathway is not highly ligand-dependent.
D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008985:Monensin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D008985:Monensin; D003513:Cycloheximide