Internalization efficiency of the transferrin receptor

Quantitative ultrastructural and biochemical methods have allowed us to obtain a coherent set of data on the internalization efficiency of the transferrin receptor (TfR). In confluent cell cultures we find that (1) the initial internalization rate of transferrin is approximately 10% per minute, and (2) around 10% of cell-surface TfRs are present in coated pits. From these data a lifetime of coated pits of ca. 1 min is derived. Furthermore, we show that coated pits constitute 1.1-1.4% of the plasma membrane area in confluent cell cultures. Thus, the TfR is concentrated six- to ninefold in coated pits compared to resident plasma membrane proteins. Moreover, we show that the concentration of TfRs in coated pits is cell density dependent, since only around 5% of the receptors are present in coated pits in low-density cultures. Correspondingly, the internalization of TfRs in high-density cell cultures is roughly twice as efficient as that in low-density cell cultures. The reduced TfR internalization efficiency at low cell density is accounted for by a concomitant decrease to 0.55% in the relative surface area occupied by coated pits.