Identification of a Human Heme Exporter that Is Essential for Erythropoiesis

@article{Quigley2004IdentificationOA,
  title={Identification of a Human Heme Exporter that Is Essential for Erythropoiesis},
  author={John G Quigley and Zhantao Yang and Mark T. Worthington and John D Phillips and Kathleen M. Sabo and Daniel E Sabath and Carl Lansing Berg and Shigeru Sassa and Brent L. Wood and Janis L. Abkowitz},
  journal={Cell},
  year={2004},
  volume={118},
  pages={757-766}
}

Figures and Tables from this paper

The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation.
TLDR
Feline leukemia virus subgroup C receptor 1 regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema, and the aberrant expression of Flvcr1 isoforms may play a role in the pathogenesis of disorders characterized by an imbalance between heme and globin synthesis.
A Heme Export Protein Is Required for Red Blood Cell Differentiation and Iron Homeostasis
TLDR
It is demonstrated that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron, and the trafficking of heme, and not just elemental iron, facilitates erythropoiesis and systemic iron balance.
Heme Exporter FLVCR Is Required for T Cell Development and Peripheral Survival
TLDR
It is suggested that heme metabolism is particularly important in the T lineage because deletion of Flvcr in murine hematopoietic precursors caused a complete block in αβ T cell development at the CD4+CD8+ double-positive stage, although other lymphoid lineages were not affected.
Cell Development and Peripheral Survival Heme Exporter FLVCR Is Required for T
TLDR
These studies identify a novel and unexpected role for FLVCR, a major facilitator superfamily metabolite transporter, in T cell development and suggest that heme metabolism is particularly important in the T lineage.
The Fowler Syndrome-Associated Protein FLVCR2 Is an Importer of Heme
TLDR
Tissue expression analysis indicates that FLVCR2 is expressed in a broad range of human tissues, including liver, placenta, brain, and kidney, which will have important implications in elucidating the pathogenic mechanisms of Fowler syndrome and of phenotypically associated disorders.
The heme exporter Flvcr1 regulates expansion and differentiation of committed erythroid progenitors by controlling intracellular heme accumulation
TLDR
Consistently, reduction or increase of the cytosolic heme rescued the erythroid defects in zebrafish deficient in Flvcr1a or FlvCr1b, respectively, suggesting heme export represents a tightly regulated process that controls erythropoiesis.
Coordinate expression of heme and globin is essential for effective erythropoiesis.
TLDR
It is shown that erythropoiesis fails when heme is excessive, and the importance of evaluating Ter119(-) erythroid cells when studying erythyroid marrow failure in murine models is emphasized.
Heme and erythropoieis: more than a structural role
TLDR
The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency.
Biology of Heme in Mammalian Erythroid Cells and Related Disorders
TLDR
The biology of heme in mammalian erythroid cells, including the heme biosynthetic pathway as well as the regulatory role of he me and human disorders that arise from defective heme synthesis are focused on.
Identification and characterization of a heme exporter from the MRP family in Drosophila melanogaster
TLDR
The findings suggest a conserved heme homeostasis mechanism within insects, and between insects and mammals, and propose the fly model may be a good complement to the existing platforms of heme studies.
...
...

References

SHOWING 1-10 OF 118 REFERENCES
A Putative Cell Surface Receptor for Anemia-Inducing Feline Leukemia Virus Subgroup C Is a Member of a Transporter Superfamily
TLDR
Results suggest that the targeted destruction of erythroblasts by FeLV-C may derive from their greater sensitivity to this virus rather than from a preferential susceptibility to infection.
Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload
TLDR
It is demonstrated that ALAS‐E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells and that the mode of iron accumulation caused by the lack of ALas‐E is different in primitive and definitive erystroid cells.
Hematopoietic target cells of anemogenic subgroup C versus nonanemogenic subgroup A feline leukemia virus
TLDR
Acute anemia induction by subgroup C FeLV does not reflect a unique tropism for marrow erythroid cells but rather indicates a unique cytopathic effect of the SU on erystroid progenitor cells.
Heme binding to Hep G2 human hepatoma cells.
Characterization of a human plasma membrane heme transporter in intestinal and hepatocyte cell lines.
TLDR
A new method for quantifying heme uptake in individual cells is established and strong evidence is provided that this uptake is a regulated, carrier-mediated process is provided.
ABCG2 (BCRP) expression in normal and malignant hematopoietic cells
TLDR
The potential usefulness of ABCG2 as a marker primitive stem cells and possible physiologic roles ofABCG2 in protection of primitive stem cell populations, and potential methods of overcoming ABCG1‐associated drug resistance in anticancer therapy are focused on.
The role of haem biosynthetic and degradative enzymes in erythroid colony development: the effect of haemin
TLDR
In vitro culture of murine bone marrow has proved to be a useful system for defining the haem biosynthetic and degradative enzymatic pathways during erythroid colony (CFU‐E) growth and development, but the observed increase in haem enzymes brought about by haemin was completely suppressed by addition of cycloheximide to the cultures.
Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells
  • S. Sassa
  • Biology, Chemistry
    The Journal of experimental medicine
  • 1976
TLDR
Data suggest that a sequential induction of the heme pathway enzyme takes place during erythroid differentiation of Friend leukemia cells, and that this induction may be due to a sequential activation of genes coding for these enzyme activities.
Molecular Characterization of a Newly Identified Heme-binding Protein Induced during Differentiation of urine Erythroleukemia Cells*
TLDR
This newly identified heme-binding protein, p22 HBP, may be involved in heme utilization for hemoprotein synthesis and even be coupled to hemoglobin synthesis during erythroid differentiation.
...
...