title: Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter.
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.
authors.affiliation: Department of Medicine, Children's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Donovan
authors.forename: A
authors.initials: A
authors.lastname: Brownlie
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Shepard
authors.forename: S J
authors.initials: SJ
authors.lastname: Pratt
authors.forename: J
authors.initials: J
authors.lastname: Moynihan
authors.forename: B H
authors.initials: BH
authors.lastname: Paw
authors.forename: A
authors.initials: A
authors.lastname: Drejer
authors.forename: B
authors.initials: B
authors.lastname: Barut
authors.forename: A
authors.initials: A
authors.lastname: Zapata
authors.forename: T C
authors.initials: TC
authors.lastname: Law
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
authors.forename: S E
authors.initials: SE
authors.lastname: Lux
authors.forename: G S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: J L
authors.initials: JL
authors.lastname: Pinkus
authors.forename: P D
authors.initials: PD
authors.lastname: Kingsley
authors.forename: J
authors.initials: J
authors.lastname: Palis
authors.forename: M D
authors.initials: MD
authors.lastname: Fleming
authors.forename: N C
authors.initials: NC
authors.lastname: Andrews
authors.forename: L I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins; D016386:Chromosome Walking; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D019143:Evolution, Molecular; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014981:Xenopus; D015017:Yolk Sac / Q000378:metabolism; D015027:Zebrafish; D000098742:Ferroportin
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D006454:Hemoglobins; D000098742:Ferroportin; D007501:Iron