Identification of a Human Heme Exporter that Is Essential for Erythropoiesis

• Published in: Cell 2004-09, Vol.118 (6), p.757-766
• Main Authors: Quigley, John G., Yang, Zhantao, Worthington, Mark T., Phillips, John D., Sabo, Kathleen M., Sabath, Daniel E., Berg, Carl L., Sassa, Shigeru, Wood, Brent L., Abkowitz, Janis L.
• Format: Article
• Language: English
• Subjects: Apoptosis - physiology; Cell Differentiation - physiology; Cell Line; Erythrocytes - metabolism; Erythropoiesis - physiology; Gene Expression Regulation, Developmental - physiology; Hematopoietic Stem Cells - metabolism; Heme - metabolism; Humans; Intestines - metabolism; Liver - metabolism; Membrane Transport Proteins - genetics; Membrane Transport Proteins - isolation & purification; Membrane Transport Proteins - metabolism; Protein Transport - physiology; Receptors, Virus - genetics; Receptors, Virus - isolation & purification; Receptors, Virus - metabolism; RNA, Messenger - metabolism; Up-Regulation - physiology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2004.08.014

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.