IRON TRANSPORTER-FUNCTIONAL CHARACTERIZATION--REGULATION

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Iron is an essential trace element for all species. It is utilized by all cells and represents an important cofactor in many proteins. Yet, if it accumulates in excessive amounts, it can catalyze the formation of dangerous organic and oxygen-based toxic radicals. Therefore, the concentration of this free transition metal in biological fluids is under tight control. In the intestine, reductants such as ascorbic acid, as well as the activity of ferrireductase enhance iron absorption, allowing iron to be transported into enterocytes via a Fe2+-specific transport system. Despite extensive studies, molecular mechanisms of intestinal iron absorption remain unknown, and an Fe2+ transporter has not yet been reported for mammals. Working in the laboratory of Dr. Hediger (my sponsor), I have recently been successful in cloning an Fe2+ transporter (IDCTl, Iron preferring Divalent Cation Transporter l) from iron deficient rat duodenum by expression cloning with Xenopus oocytes. The goal of this proposal is to characterize this transporter protein by l) elucidating the structure-function relationship of IDCTl, 2) determining the cellular and subcellular localization of IDCTl in various tissues using immunocytochemistry, and 3) investigating the regulation of IDCTI mRNA. I am also proposing to clone a putative low affinity iron transporter, as well as a zinc.