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.
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01 July 2003
In the course of repeating experiments described in the above paper, the authors have discovered that some of the confocal microscopy images presented in Figs 1 and 2 were inappropriately processed. The differences between the present confocal images and the ones published with the paper require us to revise the conclusion that TfR binding by HFE is required for endocytosis of HFE and HFE-mediated regulation of ferritin levels, and we are therefore retracting the paper.
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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.).
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Figure S1
Distributions of HFE-GFP, TfR and 5' nucleotidase in HuTu-80 cells transfected with wild-type HFE-GFP. Figure S2 Locations of the residues affected by the C260Y and W81A mutations. Figure S3 Distributions of TfR and HFE in HuTu-80 cells expressing HFE-LDLR-GFP proteins. (PDF 410 kb)
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Ramalingam, T., West, A., Lebrón, J. et al. RETRACTED ARTICLE: Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis. Nat Cell Biol 2, 953–957 (2000). https://doi.org/10.1038/35046611
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DOI: https://doi.org/10.1038/35046611
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