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
  • Membrane Proteins/metabolism
  • RNA Interference
  • Zebrafish/physiology
  • Erythrocytes/pathology
  • Caenorhabditis elegans Proteins/genetics
  • Caenorhabditis elegans Proteins/metabolism*
  • Animals
  • ATP-Binding Cassette Transporters/genetics
  • ATP-Binding Cassette Transporters/metabolism*
  • Caenorhabditis elegans/physiology
  • Erythrocytes, Abnormal/cytology
  • Heme/metabolism*
  • Protein Transport
  • RNA, Small Interfering
  • Erythropoiesis/physiology*
  • ATP Binding Cassette Transporter, Subfamily B/genetics
  • ATP Binding Cassette Transporter, Subfamily B/metabolism*
  • Multidrug Resistance-Associated Proteins/genetics
  • Multidrug Resistance-Associated Proteins/metabolism*
  • Intestines/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
Figure Gallery (1 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
abcc5WTstandard conditionsDay 4ISH
gata1aWTstandard conditionsPrim-5ISH
gata1aWTcontrolPrim-5ISH
gata1aWT + MO1-abcc5standard conditionsPrim-5Not DetectedISH
1 - 4 of 4
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Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-abcc5standard conditionsPrim-5
WT + MO1-abcc5standard conditionsProtruding-mouth
WT + MO1-abcc5standard conditionsProtruding-mouth
cz3325Tg + MO1-abcc5standard conditionsLong-pec
cz3325Tg + MO1-abcc5standard conditionsLong-pec
1 - 5 of 5
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz3325TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    abcc5MO1-abcc5MRPHLNO
    1 - 1 of 1
    Show
    Fish
    Fish
    cz3325Tg + MO1-abcc5
    WT
    WT + MO1-abcc5
    1 - 3 of 3
    Show
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Korolnek, T., Zhang, J., Beardsley, S., Scheffer, G.L., Hamza, I. (2014) Control of Metazoan Heme Homeostasis by a Conserved Multidrug Resistance Protein. Cell Metabolism. 19(6):1008-19.