The transferrin receptor and the release of iron from transferrin.

Abstract

In a classic report detailing the role of transferrin in providing iron to human reticulocytes, Jand1 and coworkers noted that uptake of transferrin-borne iron was saturable as the concentration of transferrin in the culture medium increased, and that uptake was essentially abolished if cells were first exposed to trypsin. 1 On the basis of these observations, the existence of a cell-surface receptor for transferrin was first postulated. Numerous attempts to solubilize, isolate and characterize the transferrin receptor inevitably followed, but at first with little concordance in reported findings. Ultimately, however, such efforts led to the recognition that the transferrin receptor was a disulfide-linked homodimer of 95,000 KDa glycosylated subunits’2-4 still capable of binding transferrin when solubilized in non-denaturing detergent. 5 Cloning of receptor then definitively established that its cDNA coded for an amino acid sequence of 760 residues with a calculated molecular weight of 84, 910. 6 The two chains comprising the intact receptor are joined by a pair of disulfide bonds within the intramembranous portion of the receptor, with anchoring to the membrane facilitated by a covalently-bound fatty acid residue. 7 Hydropathy analysis suggests that this intramembranous segment consists of 28 amino acids (residues 62 to 89 in the sequence); the remainder of the N-terminal sequence would then lie within the cytoplasm. The bulk of the C-terminal region bearing the transferrin-binding site is disposed extracellularly, accessible to the extracellular space. N- and O-linked oligosaccharides8,9 may serve to maintain the extracellular domain in free contact with the bathing fluid, and thereby poised to capture transferrin.