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Binding and uptake of H-ferritin are mediated by human transferrin receptor-1

Li, Li and Fang, Celia J. and Ryan, James C. and Niemi, Eréne C. and Lebrón, José A. and Bjorkman, Pamela J. and Arase, Hisashi and Torti, Frank M. and Torti, Suzy V. and Nakamura, Mary C. and Seaman, William E. (2010) Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proceedings of the National Academy of Sciences of the United States of America, 107 (8). pp. 3505-3510. ISSN 0027-8424. PMCID PMC2840523.

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Ferritin is a spherical molecule composed of 24 subunits of two types, ferritin H chain (FHC) and ferritin L chain (FLC). Ferritin stores iron within cells, but it also circulates and binds specifically and saturably to a variety of cell types. For most cell types, this binding can be mediated by ferritin composed only of FHC (HFt) but not by ferritin composed only of FLC (LFt), indicating that binding of ferritin to cells is mediated by FHC but not FLC. By using expression cloning, we identified human transferrin receptor-1 (TfR1) as an important receptor for HFt with little or no binding to LFt. In vitro, HFt can be precipitated by soluble TfR1, showing that this interaction is not dependent on other proteins. Binding of HFt to TfR1 is partially inhibited by diferric transferrin, but it is hindered little, if at all, by HFE. After binding of HFt to TfR1 on the cell surface, HFt enters both endosomes and lysosomes. TfR1 accounts for most, if not all, of the binding of HFt to mitogen-activated T and B cells, circulating reticulocytes, and all cell lines that we have studied. The demonstration that TfR1 can bind HFt as well as Tf raises the possibility that this dual receptor function may coordinate the processing and use of iron by these iron-binding molecules.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2010 by the National Academy of Sciences. Contributed by Pamela J. Björkman, November 18, 2009 (sent for review October 5, 2009). Published online before print February 4, 2010. We thank Kenneth Scalapino, M.D., for his expert advice and help with flow cytometry, and Eric Huang, M.D. for assistance with microscopy. This work was supported by National Institutes of Health Grants R01 AI061164-01A1 (to W.E.S.) and R37DK42412 (to F.M.T.) and by the Veterans Administration.
Funding AgencyGrant Number
NIHR01 AI061164-01A1
Veterans AdministrationUNSPECIFIED
Subject Keywords:ferritin; HFE; iron; receptors; endocytosis
Issue or Number:8
PubMed Central ID:PMC2840523
Record Number:CaltechAUTHORS:20100405-110249328
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17852
Deposited By: Tony Diaz
Deposited On:14 Apr 2010 19:05
Last Modified:03 Oct 2019 01:34

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