Localisation of divalent metal transporter I (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes iniron overload

Background--The mechanism of iron absorption by the intestine and its trans fer to the main iron storage site, the liver, is poorly understood. Recentl y an iron carrier was cloned and named DMT1 (divalent metal transporter 1). Aims--To determine the level of DMT1 gene expression and protein distributi on in duodenum and liver. Methods--A DMT1 cRNA and antibody were produced and used in in situ hybridi sation and immunohistochemistry, respectively, in rats in which the iron st ores were altered by feeding diets with normal, low, and high iron content. Results--Duodenal DMT1 mRNA was low in crypts and increased at the crypt-vi llus junction in iron deficient and control rats; it fell in the iron loade d state. Staining for DMT1 protein was not detected in crypts. In villus en terocytes, protein staining was localised to the microvillus membrane in ir on deficiency, in the cytoplasm and to a lesser extent in the membrane in c ontrols, and entirely in the cytoplasm of iron loaded animals. Liver DMT1 m RNA was distributed evenly across hepatocytes. DMT1 protein staining was ob served on hepatocyte plasma membranes, with highest values in the iron load ed state, lower values in control animals, and none after iron depletion. Conclusions-Results are consistent with a role for DMT1 in the transmembran e transport of non-transferrin bound iron from the intestinal lumen and fro m the portal blood.