Pumping iron: the strange partnership of the hemochromatosis protein, a class I MHC homolog, with the transferrin receptor

• Published in: Traffic (Copenhagen, Denmark) Vol. 2; no. 3; pp. 167 - 174
• Main Author: Enns, Caroline A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2001
• Subjects: Animals; beta 2-Microglobulin - chemistry; beta 2-Microglobulin - metabolism; Hemochromatosis - genetics; Hemochromatosis - metabolism; Hemochromatosis Protein; hereditary hemochromatosis; HFE; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class I - physiology; HLA Antigens - chemistry; HLA Antigens - genetics; HLA Antigens - metabolism; Homeostasis; Humans; Iron - metabolism; Membrane Proteins; Models, Biological; Protein Structure, Secondary; Receptors, Transferrin - chemistry; Receptors, Transferrin - metabolism; Transferrin; transferrin receptor
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1034/j.1600-0854.2001.020303.x

People suffering from hereditary hemochromatosis (HH) can not regulate the uptake of iron properly and gradually accumulate iron in their body over their lifetime. The protein involved in HH, HFE, has been recently identified as a class I major histocompatibility complex (MHC) homolog. The wild‐type HFE associates and co‐traffics with the transferrin receptor (TfR). The mutation responsible for 83% of HH (C260Y) results in the failure of HFE to form a critical disulfide bond, bind β2 microglobulin, bind TfR, and traffic to the cell surface. In non‐polarized cells, the partnership of HFE and TfR results in decreased iron uptake into cells. The mechanism whereby a class I MHC homolog modifies the function of a membrane receptor and how this dynamic complex of molecules regulates iron transport across intestinal epithelial cells is the subject of this review.