Abstract

Background on SFT

SFT and Surface Tf Receptors

Coordinate Synthesis of SFT & TfRs

Is SFT rate-limiting for iron uptake?

Conclusions and References

Discussion
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SFT (Stimulator of Fe Transport) is an integral membrane protein that facilitates nontransferrin-bound iron uptake. SFT is found not only on the cell surface, but also within intracellular recycling endosomes where it co-localizes with transferrin (Tf). Functionally, over-expression of SFT is found to also stimulate iron assimilation from Tf. To determine if SFT regulates Tf-mediated uptake by increasing synthesis of Tf receptors or enhancing ligand affinity, [125I]Tf binding studies were performed. Surprisingly, cells stably expressing SFT were found to have fewer Tf receptors. This result is most likely due to iron-loading promoted by the presence of the transport protein. Tf receptor synthesis is known to be down-regulated when cellular iron levels are increased; similarly, endogenous SFT synthesis becomes down-regulated in response to iron-loading. While the coordinated biosynthetic control of both molecules supports their functional relationship, the fact that over-expression of SFT stimulates Tf receptor-mediated iron assimilation suggests that this novel protein is a rate-limiting component in this pathway. Kinetic arguments are presented to support this hypothesis.

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Presentation Number SAyu0529
Keywords: iron, transport, transferrin