Transferrin-mediated cellular iron uptake

The basic model for cellular uptake of iron relies on the iron-chelating protein transferrin (Tf), which is capable of binding iron under one set of conditions and releasing it under another set of conditions. Tf has specific membrane receptors on the surface of the cells that require iron. Tf-receptor binding is followed by internalization through a system of coated pits and vesicles. The rapid decline of pH of these vesicles leads to release and sequestration of iron by the cell. Apotransferrin-receptor complex returns to the cell surface, where, under neutral pH conditions, apotransferrin is dissociated. Other models for cellular uptake of iron include extraction of iron from Tf on the cell surface without internalization, uptake by adsorptive mechanism, and fluid-phase endocytosis. Recent advances in cellular and molecular biology, gene cloning, and monoclonal antibody technique have elucidated many features of these processes at a molecular level. These advances are reviewed and prospects for future work discussed.