Functional properties of transfected human DMT1 iron transporter

Recently, mutation of the DMT1 gene has been discovered to cause ineffectiv e intestinal iron uptake and abnormal body iron metabolism in the anemic Be lgrade rat and mk mouse. DMT1 transports first-series transition metals, bu t only iron turns on an inward proton current. The process of iron transpor t was studied by transfection of human DMT1 into the COS-7 cell line. Nativ e and epitope-tagged human DMT1 led to increased iron uptake. The human gen e with the Belgrade rat mutation was found to have one-fifth of the activit y 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 transpo rter demonstrates uptake without saturation from 0 to 50 muM iron, recapitu lating earlier studies of isolated intestinal enterocytes. Diethylpyrocarbo nate inhibition of iron uptake in DMT1-transfected cells suggests a functio nal role for histidine residues. Finally, a model is presented that incorpo rates the selectivity of the DMT1 transporter for transition metals and a p otential role for the inward proton current.