Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis

T. S. Ramalingam, Anthony P. West, José A. Lebrón, Jasvinder S. Nangiana, Thomas H. Hogan, Caroline A. Enns, Pamela J. Bjorkman

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)953-957
Number of pages5
JournalNature Cell Biology
Volume2
Issue number12
DOIs
StatePublished - Dec 18 2000

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis'. Together they form a unique fingerprint.

  • Cite this

    Ramalingam, T. S., West, A. P., Lebrón, J. A., Nangiana, J. S., Hogan, T. H., Enns, C. A., & Bjorkman, P. J. (2000). Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis. Nature Cell Biology, 2(12), 953-957. https://doi.org/10.1038/35046611