The Hereditary Hemochromatosis protein HFE and its chaperone β2-microglobulin localise predominantly to the endosomal-recycling compartment

Hereditary Hemochromatosis is an iron overload disease most frequently associated with mutations in the HFE gene. While clinical studies of the disease have received extensive attention by various groups, the localisation, trafficking and function of the HFE protein, and its chaperone beta 2-microglobulin (beta 2M), require further investigation. In this study, we present data on the cellular localisation of HFE and its clinically relevant mutants in HuTu 80 cells. We find by confocal microscopy that HTE localises to the endosomal-recycling compartment (ERC), with minimal localisation to sorting or late endosomes. Interestingly, we also demonstrate that beta 2M localises to the ERC where it co-localises with HFE. We find that exogenous expression of HFE results in enhanced beta 2M cellular levels and that beta 2M is necessary for cell surface expression of HFE. Finally, we have analysed the functional effects of exogenous expression of HFE and beta 2M on transferrin binding to the cell surface. In summary, our study sheds light on the localisation and functional effects of the HFE and its chaperone protein beta 2M. (c) 2007 Elsevier Inc. All rights reserved.