The behavior of transferrin receptors in rat hepatocyte plasma membranes.

The liver serves as a storage organ for iron, 2-5 mg of Fe being exchanged between plasma and liver daily in the human being. Such iron transfer from serotransferrin (TF) to hepatocytes involves a TF receptor. We are reporting some of the properties of this receptor using isolated rat hepatocyte membranes as the receptor source. Iron-saturated 125I-rat TF was used for these studies. Specific versus nonspecific TF binding was evaluated by labelling the membranes with 125I-TF and then displacing specific binding with excess unlabelled TF. A mean residency time of 18-20 min was calculated for the TF on each receptor molecule. There were 31,000 +/- 17,000 receptors/cell with a dissociation constant of 0.3 X 10(-7) mol/l. The binding obeyed simple Michaelis-Menten kinetics. Specifically bound iron-saturated 125I-TF could best be eluted with cold Fe-saturated TF; cold apo- and 50% saturated TFs were less effective. The binding of apo- and 50% saturated TF was much less pronounced than that of Fe-saturated TF. The membrane receptor was moderately heat stable, extractable with detergent, and was trypsin sensitive. Studies with 125I/59Fe-TF and whole cells suggested that Fe-TF is not in a major way internalized during iron uptake. It is concluded that there are TF receptors present on the rat hepatocyte plasma membrane that may have a role in uptake by the cells without internalization of the TF molecule.