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| Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter |
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| Author(s): Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI |
| Source: NATURE Volume: 403 Issue: 6771 Pages: 776-781 Published: FEB 17 2000 |
| Times Cited: 607 References: 29 |
| 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 1-3). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Zon, LI (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA |
Addresses:
1. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA
2. Dana Farber Canc Inst, Boston, MA 02115 USA
3. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA
4. Washington Univ, Sch Med, St Louis, MO 63110 USA
5. Univ Complutense, Fac Biol, Dept Cell Biol, E-28040 Madrid, Spain
6. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA
7. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
8. Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA
9. Univ Rochester, Med Ctr, Ctr Canc, Rochester, NY 14642 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 286BE |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |