Role of microtubules in transferrin receptor transport from the cell surface to endosomes and the Golgi complex.
Transferrin receptor (TfR) follows complex pathways of transport after endocytosis from the cell surface. Most TfR is transported to endosomes and returns rapidly to the cell surface. In addition, approximately 10% of the internalized receptor recycles through the Golgi complex. To examine the role of microtubules in TfR traffic, K562 cultured human leukemia cells treated with nocodazole to depolymerize microtubules were studied. Nocodazole caused a 50% increase in the level of surface TfR, which was due to a change in receptor dynamics. The endocytosis rate in treated cells was 20% of control, indicating that TfR endocytosis via clathrin-coated vesicles was slowed, whereas the recycling of internalized receptors to the cell surface was unaffected. In contrast, nocodazole had little effect on the transport of TfR from the cell surface to the Golgi complex. Thus, the fragmentation and dispersal of the Golgi complex caused by microtubule depolymerization, which does not interrupt secretory traffic through this organelle, also does not block recycling through the Golgi. The decreased TfR endocytosis via coated vesicles and the increased TfR transport to the Golgi caused by nocodazole suggest that either (i) endocytosis via coated vesicles is not the rate-limiting step in transport to the Golgi or (ii) coated vesicles are not a part of this pathway. Finally, because nocodazole inhibits traffic from endosomes to lysosomes, surface-to-Golgi transport probably does not involve a lysosomal intermediate.
Jin
M
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Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4935.
Snider
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MD
D005089:Exocytosis; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D015388:Organelles / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D011990:Receptors, Transferrin; D012794:Sialic Acids; D014168:Transferrin; D006735:Horseradish Peroxidase; D015739:Nocodazole