Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter

Adriana Donovan, Alison Brownlie, Yi Zhou, Jennifer Shepard, Stephen J. Pratt, John Moynihan, Barry H. Paw, Anna Drejer, Bruce Barut, Agustin Zapata, Terence C. Law, Carlo Brugnara, Samuel E. Lux, Geraldine S. Pinkus, Jack L. Pinkus, Paul D. Kingsley, James Palis, Mark D. Fleming, Nancy C. Andrews and Leonard I. Zon ()
Additional contact information
Adriana Donovan: Children's Hospital and Dana-Farber Cancer Institute
Alison Brownlie: Children's Hospital and Dana-Farber Cancer Institute
Yi Zhou: Children's Hospital and Dana-Farber Cancer Institute
Jennifer Shepard: Children's Hospital and Dana-Farber Cancer Institute
Stephen J. Pratt: Washington University School of Medicine
John Moynihan: Children's Hospital and Dana-Farber Cancer Institute
Barry H. Paw: Children's Hospital and Dana-Farber Cancer Institute
Anna Drejer: Children's Hospital and Dana-Farber Cancer Institute
Bruce Barut: Children's Hospital and Dana-Farber Cancer Institute
Agustin Zapata: Faculty of Biology, Complutense University
Terence C. Law: Children's Hospital
Carlo Brugnara: Children's Hospital
Samuel E. Lux: Children's Hospital and Dana-Farber Cancer Institute
Geraldine S. Pinkus: Brigham and Women's Hospital
Jack L. Pinkus: Brigham and Women's Hospital
Paul D. Kingsley: University of Rochester Medical Center
James Palis: University of Rochester Medical Center
Mark D. Fleming: Children's Hospital and Dana-Farber Cancer Institute
Nancy C. Andrews: Children's Hospital and Dana-Farber Cancer Institute
Leonard I. Zon: Children's Hospital and Dana-Farber Cancer Institute

Nature, 2000, vol. 403, issue 6771, 776-781

Abstract: 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, DMT1 (refs 1,2,3). 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.

Date: 2000
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DOI: 10.1038/35001596

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