PUBLICATION

Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter

Authors
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S.J., Moynihan, J., Paw, B.H., Drejer, A., Barut, B., Zapata, A., Law, T.C., Brugnara, C., Lux, S.E., Pinkus, G.S., Pinkus, J.L., Kingsley, P.D., Palis, J., Fleming, M.D., Andrews, N.C., and Zon, L.I.
ID
ZDB-PUB-000309-34
Date
2000
Source
Nature   403(6771): 776-781 (Journal)
Registered Authors
Barut, Bruce, Brownlie, Alison J., Donovan, Adriana, Paw, Barry, Pratt, Stephen J., Shepard, Jennifer, Zhou, Yi, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins/genetics*
  • Carrier Proteins/metabolism
  • Cation Transport Proteins*
  • Chromosome Walking
  • Cloning, Molecular
  • Embryo, Nonmammalian/metabolism
  • Enterocytes/metabolism
  • Erythrocytes/metabolism
  • Evolution, Molecular*
  • Hemoglobins/metabolism
  • Humans
  • Intestines/metabolism
  • Iron/blood
  • Iron/metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Open Reading Frames
  • Phenotype
  • Placenta/metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Xenopus
  • Yolk Sac/metabolism
  • Zebrafish
PubMed
10693807 Full text @ Nature
Abstract
Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of polarized duodenal enterocytes is mediated by the divalent metal transporter, DMTi. A second transporter has been postulated to export iron across the basolateral surface to the circulation. Here we have used positional cloning to identify the gene responsible for the hypochromic anaemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a multiple-transmembrane domain protein, expressed in the yolk sac, that is a candidate for the elusive iron exporter. Zebrafish ferroportin1 is required for the transport of iron from maternally derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. Human Ferroportin1 is found at the basal surface of placental syncytiotrophoblasts, suggesting that it also transports iron from mother to embryo. Mammalian Ferroportin1 is expressed at the basolateral surface of duodenal enterocytes and could export cellular iron into the circulation. We propose that Ferroportin1 function may be perturbed in mammalian disorders of iron deficiency or overload.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes