Iron homeostasis: new tales from the crypt.
The enterocyte is a highly specialized cell of the duodenal epithelium that coordinates iron uptake and transport into the body. Until recently, the molecular mechanisms underlying iron absorption and iron homeostasis have remained a mystery. This review focuses on the proteins and regulatory mechanisms known to be present in the enterocyte precursor cell and in the mature enterocyte. The recent cloning of a basolateral iron transporter and investigations into its regulation provide new insights into possible mechanisms for iron transport and homeostasis. The roles of proteins such as iron regulatory proteins, the hereditary hemochromatosis protein (HFE)-transferrin receptor complex, and hephaestin in regulating this transporter and in regulating iron transport across the intestinal epithelium are discussed. A speculative, but testable, model for the maintenance of iron homeostasis, which incorporates the changes in the iron-related proteins associated with the life cycle of the enterocyte as it journeys from the crypt to the tip of the villous is proposed.
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Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
Enns
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D000747:Anemia, Hypochromic / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D002454:Cell Differentiation; D016764:Cell Polarity; D004386:Duodenum / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005293:Ferritins; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D007501:Iron; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human; C103673:HFE protein, human