Background and objectives: Ferroportin-1 (FPN1) is expressed in various types of cells that play critical roles in mammalian iron metabolism and appears to act as an iron exporter in these tissues. The aim of this study was to investigate whether erythroid cells possess specific mechanisms for iron export.
Design and methods: The expression of FPN1 during human erythroid differentiation, the characterization of alternative transcripts, the modulation by iron and the subcellular localization of this protein were studied.
Results: FPN1 mRNA and protein are highly expressed during human erythroid differentiation. The iron-responsive element (IRE) in the 5'- untranslated region (UTR) of FPN1 mRNA is functional but, in spite of that, FPN1 protein expression, as well as mRNA level and half-life, seem not to be affected by iron. To explain these apparenthy discordant results we searched for alternative transcripts of FPN1 and found at least three different types of transcripts, displaying alternative 5' ends. Most of the FPN1 transcripts code for the canonical protein, but only half of them contain an IRE in the 5'-UTR and have the potential to be translationally regulated by iron. Expression analysis shows that alternative FPN1 transcripts are differentially expressed during erythroid differentiation. Finally, sustained expression of alternative FPN1 transcripts is apparently observed only in erythroid cells.
Interpretation and conclusions: This is the first report describing the presence of FPN1 in erythroid cells at all stages of differentiation, providing evidence that erythroid cells possess specific mechanisms of iron export. The existence of multiple FPN1 transcripts indicates a complex regulation of the FPN1 gene in erythroid cells.