Document Detail


ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin.
MedLine Citation:
PMID:  20682781     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ningning Zhao; Junwei Gao; Caroline A Enns; Mitchell D Knutson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2010-12-07     Revised Date:  2014-06-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32141-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cation Transport Proteins / genetics,  metabolism*
Cell Line
Endosomes / metabolism
Hepatocytes / metabolism
Humans
Hydrogen-Ion Concentration
Iron / metabolism*
Mice
RNA, Small Interfering / metabolism
Transferrin / metabolism*
Grant Support
ID/Acronym/Agency:
DK 054488/DK/NIDDK NIH HHS; DK 080706/DK/NIDDK NIH HHS; T32 DK067864/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cation Transport Proteins; 0/RNA, Small Interfering; 0/SLC39A14 protein, human; 0/SLC39A14 protein, mouse; 0/Transferrin; 0/solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2; E1UOL152H7/Iron
Comments/Corrections

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