A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.
Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells. Ireg1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA contains a functional iron-responsive element (IRE). IREG1 stimulates iron efflux following expression in Xenopus oocytes. We conclude that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease, hereditary hemochromatosis.
McKie
A T
AT
Department of Molecular Medicine, King's College London, Guy's, King's, St Thomas' School of Medicine, United Kingdom. amckie@hgmp.mrc.ac.uk
Marciani
P
P
Rolfs
A
A
Brennan
K
K
Wehr
K
K
Barrow
D
D
Miret
S
S
Bomford
A
A
Peters
T J
TJ
Farzaneh
F
F
Hediger
M A
MA
Hentze
M W
MW
Simpson
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D027682:Cation Transport Proteins; D002451:Cell Compartmentation; D016764:Cell Polarity; D003001:Cloning, Molecular; D004386:Duodenum / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D005786:Gene Expression Regulation; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011169:Portal Vein / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014168:Transferrin / Q000172:deficiency; D000098742:Ferroportin
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005290:Ferric Compounds; D008565:Membrane Proteins; D012333:RNA, Messenger; D014168:Transferrin; D000098742:Ferroportin; D007501:Iron