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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-02-0425. This Article Full Text (PDF) All Versions of this Article: 2003-02-0425v1 102/5/1884    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Forbes, J. R Articles by Gros, P. Search for Related Content PubMed PubMed Citation Articles by Forbes, J. R Articles by Gros, P. Social Bookmarking                   What's this? Submitted February 7, 2003 Accepted May 6, 2003 Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane John R Forbes and Philippe Gros* Biochemistry, McGill University, Montreal, Quebec, Canada; Center for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada; Cancer Center, McGill University, Montreal, Quebec, Canada * Corresponding author; email: philippe.gros{at}mcgill.ca. Mutations in the Nramp1 gene (Slc11a1) cause susceptibility to infection by intracellular pathogens. The Nramp1 protein is expressed at the phagosomal membrane of macrophages and neutrophils, and is a paralogue of the Nramp2 (Slc11a2) iron transporter. The Nramp1 transport mechanism at the phagosomal membrane has remained controversial. An Nramp1 protein modified by insertion of a haemagglutinin epitope into the predicted TM7/8 loop was expressed at the plasma membrane of CHO cells as demonstrated by immunofluorescence and surface biotinylation. Experiments in Nramp1HA transfectants using the metal-sensitive fluorophors Calcein and Fura2 showed that Nramp1HA can mediate Fe2+, Mn2+, and Co2+ uptake. Similar results were obtained in transport studies using radioisotopic 55Fe2+ and 54Mn2+. Nramp1HA transport was dependent on time, temperature, and acidic pH, occurring down the proton gradient. These experiments suggest that Nramp1HA may be a more efficient transporter of Mn2+ compared to Fe2+, and a more efficient Mn2+ transporter than Nramp2HA. The membrane topology and transport properties of Nramp1HA and Nramp2HA were indistinguishable, suggesting that Nramp1 divalent-metal transport at the phagosomal membrane is mechanistically similar to that of Nramp2 at the membrane of acidified endosomes. 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