@article{096f9424653646dc955125bdc78e8cf1,
title = "Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis",
abstract = "HFE, the protein that is mutated in hereditary haemochromatosis, binds to the transferrin receptor (TfR). Here we show that wild-type HFE and TfR localize in endosomes and at the basolateral membrane of a polarized duodenal epithelial cell line, whereas the primary haemochromatosis HFE mutant, and another mutant with impaired TfR-binding ability accumulate in the ER/Golgi and at the basolateral membrane, respectively. Levels of the iron-storage protein ferritin are greatly reduced and those of TfR are slightly increased in cells expressing wild-type HFE, but not in cells expressing either mutant. Addition of an endosomal-targeting sequence derived from the human low-density lipoprotein receptor (LDLR) to the TfR. binding-impaired mutant restores its endosomal localization but not ferritin reduction or TfR elevation. Thus, binding to TfR is required for transport of HFE to endosomes and regulation of intracellular iron homeostasis, but not for basolateral surface expression of HFE.",
author = "Ramalingam, {T. S.} and West, {Anthony P.} and Lebr{\'o}n, {Jos{\'e} A.} and Nangiana, {Jasvinder S.} and Hogan, {Thomas H.} and Enns, {Caroline A.} and Bjorkman, {Pamela J.}",
note = "Funding Information: ACKNOWLEDGEMENTS We thank R. Diamond (Caltech Cell Sorting Facility) for assistance with flow cytometry, M. Bennett and M. Murphy for help with figures, W. L. Martin for the EGFP-Bluescript vector, D. Anderson for use of the confocal microscope, K. Zinn and L. Weiner for helpful discussions, and J. Feder and members of the Bjorkman laboratory for critical reading of the manuscript. This work was supported by the W. M. Keck Foundation Fund for Discovery in Basic Medical Research (to P.J.B.), the NIH (grant no. DK54488 to C.A.E.), and the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation (grant no. DRG-1445 to A.P.W.). Correspondence and requests for materials should be addressed to P.J.B. Supplementary Information is available on Nature Cell Biology{\textquoteright}s website (http://www.cellbio.nature.com) or as paper copy from the London editorial office of Nature Cell Biology.",
year = "2000",
month = nov,
day = "14",
doi = "10.1038/35046611",
language = "English (US)",
volume = "2",
pages = "953--957",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "12",
}