A novel mammalian iron-regulated protein involved in intracellular iron metabolism

We have isolated and characterized a novel iron-regulated gene that is homo logous to the divalent metal transporter 1 family of metal transporters. Th is gene, termed metal transporter protein (mtp1), is expressed in tissues i nvolved in body iron homeostasis including the developing and mature reticu loendothelial system, the duodenum, and the pregnant uterus. MTP1 is also e xpressed in muscle and central nervous system cells in the embryo. At the s ubcellular level, MTP1 is localized to the basolateral membrane of the duod enal epithelial cell and a cytoplasmic compartment of reticuloendothelial s ystem cells. Overexpression of MTP1 in tissue culture cells results in intr acellular iron depletion. In the adult mouse, MTP1 expression in the liver and duodenum are reciprocally regulated. Iron deficiency induces MTP1 expre ssion in the duodenum but down-regulates expression in the liver. These dat a indicate that MTP1 is an iron-regulated membrane-spanning protein that is involved in intracellular iron metabolism.