title: Interactions of the ectodomain of HFE with the transferrin receptor are critical for iron homeostasis in cells.
abstract: Expression of wild type HFE reduces the ferritin levels of cells in culture. In this report we demonstrate that the predominant hereditary hemochromatosis mutation, C282Y(2) HFE, does not reduce ferritin expression. However, the second mutation, H63D HFE, reduces ferritin expression to a level indistinguishable from cells expressing wild type HFE. Further, two HFE cytoplasmic domain mutations engineered to disrupt potential signal transduction, S335M and Y342C, were functionally indistinguishable from wild type HFE in this assay, as was soluble HFE. These results implicate a role for the interaction of HFE with the transferrin receptor in lowering cellular ferritin levels.
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Roy
authors.forename: E J
authors.initials: EJ
authors.lastname: Carlson
authors.forename: E L
authors.initials: EL
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Basava
authors.forename: S M
authors.initials: SM
authors.lastname: Starnes
authors.forename: J N
authors.initials: JN
authors.lastname: Feder
authors.forename: C A
authors.initials: CA
authors.lastname: Enns
mesh_terms: D002460:Cell Line; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D007501:Iron