PUBLICATION

Control of Metazoan Heme Homeostasis by a Conserved Multidrug Resistance Protein

Authors
Korolnek, T., Zhang, J., Beardsley, S., Scheffer, G.L., Hamza, I.
ID
ZDB-PUB-140520-10
Date
2014
Source
Cell Metabolism   19(6): 1008-19 (Journal)
Registered Authors
Hamza, Iqbal
Keywords
none
MeSH Terms
  • Protein Transport
  • Erythropoiesis/physiology*
  • Animals
  • RNA, Small Interfering
  • ATP Binding Cassette Transporter, Subfamily B/genetics
  • ATP Binding Cassette Transporter, Subfamily B/metabolism*
  • Multidrug Resistance-Associated Proteins/genetics
  • Multidrug Resistance-Associated Proteins/metabolism*
  • Caenorhabditis elegans/physiology
  • RNA Interference
  • Caenorhabditis elegans Proteins/genetics
  • Caenorhabditis elegans Proteins/metabolism*
  • ATP-Binding Cassette Transporters/genetics
  • ATP-Binding Cassette Transporters/metabolism*
  • Membrane Proteins/metabolism
  • Erythrocytes/pathology
  • Erythrocytes, Abnormal/cytology
  • Intestines/metabolism
  • Zebrafish/physiology
  • Heme/metabolism*
(all 20)
PubMed
24836561 Full text @ Cell Metab.
Abstract
Several lines of evidence predict that specific pathways must exist in metazoans for the escorted movement of heme, an essential but cytotoxic iron-containing organic ring, within and between cells and tissues, but these pathways remain obscure. In Caenorhabditis elegans, embryonic development is inextricably dependent on both maternally derived heme and environmentally acquired heme. Here, we show that the multidrug resistance protein MRP-5/ABCC5 likely acts as a heme exporter, and targeted depletion of mrp-5 in the intestine causes embryonic lethality. Transient knockdown of mrp5 in zebrafish leads to morphological defects and failure to hemoglobinize red blood cells. MRP5 resides on the plasma membrane and endosomal compartments and regulates export of cytosolic heme. Together, our genetic studies in worms, yeast, zebrafish, and mammalian cells identify a conserved, physiological role for a multidrug resistance protein in regulating systemic heme homeostasis. We envision other MRP family members may play similar unanticipated physiological roles in animal development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz3325TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    abcc5MO1-abcc5MRPHLNO
    1 - 1 of 1
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    Fish
    1 - 3 of 3
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available