| ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. | |
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MedLine Citation:
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PMID: 20682781 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ZIP14 is a transmembrane metal ion transporter that is abundantly expressed in the liver, heart, and pancreas. Previous studies of HEK 293 cells and the hepatocyte cell lines AML12 and HepG2 established that ZIP14 mediates the uptake of non-transferrin-bound iron, a form of iron that appears in the plasma during pathologic iron overload. In this study we investigated the role of ZIP14 in the cellular assimilation of iron from transferrin, the circulating plasma protein that normally delivers iron to cells by receptor-mediated endocytosis. We also determined the subcellular localization of ZIP14 in HepG2 cells. We found that overexpression of ZIP14 in HEK 293T cells increased the assimilation of iron from transferrin without increasing levels of transferrin receptor 1 or the uptake of transferrin. To allow for highly specific and sensitive detection of endogenous ZIP14 in HepG2 cells, we used a targeted knock-in approach to generate a cell line expressing a FLAG-tagged ZIP14 allele. Confocal microscopic analysis of these cells detected ZIP14 at the plasma membrane and in endosomes containing internalized transferrin. HepG2 cells in which endogenous ZIP14 was suppressed by siRNA assimilated 50% less iron from transferrin compared with controls. The uptake of transferrin, however, was unaffected. We also found that ZIP14 can mediate the transport of iron at pH 6.5, the pH at which iron dissociates from transferrin within the endosome. These results suggest that endosomal ZIP14 participates in the cellular assimilation of iron from transferrin, thus identifying a potentially new role for ZIP14 in iron metabolism. |
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Authors:
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Ningning Zhao; Junwei Gao; Caroline A Enns; Mitchell D Knutson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-03 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-11 Completed Date: 2010-12-07 Revised Date: 2011-10-17 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 32141-50 Citation Subset: IM |
Affiliation:
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Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida 32611, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cation Transport Proteins / genetics, metabolism* Cell Line Endosomes / metabolism Hepatocytes / metabolism Humans Hydrogen-Ion Concentration Iron / metabolism* Mice RNA, Small Interfering / metabolism Transcription Factors / genetics, metabolism Transferrin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK 054488/DK/NIDDK NIH HHS; DK 080706/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cation Transport Proteins; 0/DMRT1 protein; 0/RNA, Small Interfering; 0/SLC39A14 protein, human; 0/SLC39A14 protein, mouse; 0/Transcription Factors; 11096-37-0/Transferrin; 7439-89-6/Iron |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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