Identification of a Human Heme Exporter that Is Essential for Erythropoiesis

The Rockefeller University, New York, New York, United States
Cell (Impact Factor: 32.24). 10/2004; 118(6):757-66. DOI: 10.1016/j.cell.2004.08.014
Source: PubMed


FLVCR, a member of the major facilitator superfamily of transporter proteins, is the cell surface receptor for feline leukemia virus, subgroup C. Retroviral interference with FLVCR display results in a loss of erythroid progenitors (colony-forming units-erythroid, CFU-E) and severe anemia in cats. In this report, we demonstrate that human FLVCR exports cytoplasmic heme and hypothesize that human FLVCR is required on developing erythroid cells to protect them from heme toxicity. Inhibition of FLVCR in K562 cells decreases heme export, impairs their erythroid maturation and leads to apoptosis. FLVCR is upregulated on CFU-E, indicating that heme export is important in primary cells at this stage. Studies of FLVCR expression in cell lines suggest this exporter also impacts heme trafficking in intestine and liver. To our knowledge, this is the first description of a mammalian heme transporter.

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    • "Transporters may contribute to virus infection. Some researches indicated that the virus could interact with the host by binding proteins of MFS member, like FLVCR for feline leukemia virus C (FeLV-C) [16] [17]. "
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    • "P-glycoprotein-5 (EHI_125030) shows homology with the PvdE siderophore pyoverdin exporter in Pseudomonas aeruginosa [36] (Figure S3 in File S1). Moreover, MFT (EHI_173950) shows similarities with both MFS1 (the azotochelin siderophore exporter in Azotobacter vineldii [37]) and FLVCR1 (a human cytoplasmic heme exporter) [38], [39]. Furthermore, MFT is overexpressed in response to L-cysteine deprivation, which suggests that it is involved in metabolite intake or efflux in E. histolytica [40]. "
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    • "Placenta has been shown to express high amounts of FLVCR1 (Jaacks et al., 2011) but the functional roles of this molecule in this tissue are poorly investigated. FLVCR1 is required for erythroid differentiation maintaining the balance of intracellular free heme during erythropoiesis (Quigley et al., 2004) and has an important role in iron recycling by macrophages (Keel et al., 2008). It has been suggested that expression of FLVCR1 in the placenta may reverse the flow of heme from this tissue to maternal circulation, so to prevent the fetoplacental unit from iron toxicity (Cao and O'Brien, 2013). "
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