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 endosom es 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 huma n 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 endocyto sis 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 s urface to the Golgi complex. Thus, the fragmentation and dispersal of the Golgi complex caused by microtubule depolymerization, which does n ot interrupt secretory traffic through this organelle, also does not b lock recycling through the Golgi. The decreased TfR endocytosis via co ated vesicles and the increased TfR transport to the Golgi caused by n ocodazole suggest that either (i) endocytosis via coated vesicles is n ot the rate-limiting step in transport to the Golgi or (ii) coated ves icles are not a part of this pathway. Finally, because nocodazole inhi bits traffic from endosomes to lysosomes, surface-to-Golgi transport p robably does not involve a lysosomal intermediate.