Erythropoiesis and transferrin receptors

The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. Recently, it has been demonstrated that TfR1 could also have signaling functions in erythroid cells. Moreover, the second transferrin receptor, TfR2, whose signaling functions in hepatic cells are well established, was recently shown to be a partner of the erythropoietin receptor (EpoR) and thereby likely to play a role in erythroid differentiation.

This review reports recent findings regarding the specificities of the regulation of TfR1 expression and iron uptake in erythroblasts. The newly discovered noncanonical actions of TfR1 and TfR2 in erythroid cells are also discussed.

Erythrocytes contain more than 60% of the iron of the body and each day, differentiating erythroid cells uptake around 20 mg of iron for heme synthesis. Accordingly, TfR1 is one of the most abundant membrane proteins of the erythroblasts and it is not surprising that specific regulations regarding both its expression and its mechanism of action operate in erythroblasts. The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation.