title: Functional properties of transfected human DMT1 iron transporter.
abstract: Recently, mutation of the DMT1 gene has been discovered to cause ineffective intestinal iron uptake and abnormal body iron metabolism in the anemic Belgrade rat and mk mouse. DMT1 transports first-series transition metals, but only iron turns on an inward proton current. The process of iron transport was studied by transfection of human DMT1 into the COS-7 cell line. Native and epitope-tagged human DMT1 led to increased iron uptake. The human gene with the Belgrade rat mutation was found to have one-fifth of the activity of the wild-type protein. The pH optimum of human DMT1 iron uptake was 6.75, which is equivalent to the pH of the duodenal brush border. The transporter demonstrates uptake without saturation from 0 to 50 microM iron, recapitulating earlier studies of isolated intestinal enterocytes. Diethylpyrocarbonate inhibition of iron uptake in DMT1-transfected cells suggests a functional role for histidine residues. Finally, a model is presented that incorporates the selectivity of the DMT1 transporter for transition metals and a potential role for the inward proton current.
authors.affiliation: Digestive Health Research Center, Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908-0708, USA. mtw3p@virginia.edu
authors.forename: M T
authors.initials: MT
authors.lastname: Worthington
authors.forename: L
authors.initials: L
authors.lastname: Browne
authors.forename: E H
authors.initials: EH
authors.lastname: Battle
authors.forename: R Q
authors.initials: RQ
authors.lastname: Luo
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D027682:Cation Transport Proteins; D018628:Gene Dosage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D033862:Iron-Binding Proteins; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D051381:Rats; D014162:Transfection; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D000099236:Solute Carrier Family 11, Member 2