title: Identification of a human heme exporter that is essential for erythropoiesis.
abstract: 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.
authors.affiliation: Department of Medicine/Hematology, University of Washington, Seattle 98195, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Quigley
authors.forename: Zhantao
authors.initials: Z
authors.lastname: Yang
authors.forename: Mark T
authors.initials: MT
authors.lastname: Worthington
authors.forename: John D
authors.initials: JD
authors.lastname: Phillips
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Sabo
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sabath
authors.forename: Carl L
authors.initials: CL
authors.lastname: Berg
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sassa
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.forename: Janis L
authors.initials: JL
authors.lastname: Abkowitz
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004912:Erythrocytes / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C492690:FLVCR1 protein, human; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; C074548:feline leukemia virus receptor; D006418:Heme