title: The hereditary hemochromatosis protein HFE and its chaperone beta2-microglobulin localise predominantly to the endosomal-recycling compartment.
abstract: 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 beta2-microglobulin (beta2M), 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 HFE localises to the endosomal-recycling compartment (ERC), with minimal localisation to sorting or late endosomes. Interestingly, we also demonstrate that beta2M localises to the ERC where it co-localises with HFE. We find that exogenous expression of HFE results in enhanced beta2M cellular levels and that beta2M is necessary for cell surface expression of HFE. Finally, we have analysed the functional effects of exogenous expression of HFE and beta2M 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 beta2M.
authors.affiliation: Molecular Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Bhatt
authors.forename: Conor P
authors.initials: CP
authors.lastname: Horgan
authors.forename: Melanie
authors.initials: M
authors.lastname: Walsh
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000737:chemistry; D009154:Mutation; D011990:Receptors, Transferrin / Q000737:chemistry; D014168:Transferrin / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011990:Receptors, Transferrin; D014168:Transferrin; D001613:beta 2-Microglobulin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C103673:HFE protein, human