Document Detail


The role of ubiquitination in hepcidin-independent and hepcidin-dependent degradation of ferroportin.
MedLine Citation:
PMID:  22019085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The iron exporter ferroportin (Fpn) is essential to transfer iron from cells to plasma. Systemic iron homeostasis in vertebrates is regulated by the hepcidin-mediated internalization of Fpn. Here, we demonstrate a second route for Fpn internalization; when cytosolic iron levels are low, Fpn is internalized in a hepcidin-independent manner dependent upon the E3 ubiquitin ligase Nedd4-2 and the Nedd4-2 binding protein Nfdip-1. Retention of cell-surface Fpn through reductions in Nedd4-2 results in cell death through depletion of cytosolic iron. Nedd4-2 is also required for internalization of Fpn in the absence of ferroxidase activity as well as for the entry of hepcidin-induced Fpn into the multivesicular body. C. elegans lacks hepcidin genes, and C. elegans Fpn expressed in mammalian cells is not internalized by hepcidin but is internalized in response to iron deprivation in a Nedd4-2-dependent manner, supporting the hypothesis that Nedd4-2-induced internalization of Fpn is evolutionarily conserved.
Authors:
Ivana De Domenico; Eric Lo; Baoli Yang; Tamara Korolnek; Iqbal Hamza; Diane McVey Ward; Jerry Kaplan
Related Documents :
9222815 - Bicarbonate-dependent proton extrusion in chinese hamster ovary (cho) cells adapted to ...
18600935 - Effects of electroconductive heat treatment and electrical pretreatment on thermal deat...
21508665 - Augmented damage of islets by impaired exocrine acinar cells undergoing apoptosis that ...
15304155 - Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer c...
23634255 - Bridges between cell cycle regulation and self-renewal maintenance.
15966765 - Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Retracted Publication     Date:  2011-10-20
Journal Detail:
Title:  Cell metabolism     Volume:  14     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-07     Completed Date:  2012-02-24     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  635-46     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antimicrobial Cationic Peptides / deficiency,  genetics
Biological Evolution
Caenorhabditis elegans
Carrier Proteins / genetics,  metabolism*
Cation Transport Proteins / genetics,  metabolism*
Cells, Cultured
Endosomal Sorting Complexes Required for Transport / genetics,  metabolism*
HEK293 Cells
Homeostasis / physiology
Humans
Iron / metabolism*
Macrophages / cytology,  metabolism
Membrane Proteins / genetics,  metabolism*
Mice
Mice, Knockout
Plasmids
RNA, Small Interfering
Recombinant Fusion Proteins / genetics,  metabolism*
Signal Transduction / physiology*
Transfection
Ubiquitin-Protein Ligases / genetics,  metabolism*
Ubiquitination
Grant Support
ID/Acronym/Agency:
DK070947/DK/NIDDK NIH HHS; DK090257/DK/NIDDK NIH HHS; R01 DK070947-07/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Carrier Proteins; 0/Cation Transport Proteins; 0/Endosomal Sorting Complexes Required for Transport; 0/Membrane Proteins; 0/NDFIP1 protein, human; 0/Ndfip1 protein, mouse; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 0/hepcidin; 0/metal transporting protein 1; 7439-89-6/Iron; EC 6.3.2.19/Nedd4 ubiquitin protein ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections
Retraction In:
Cell Metab. 2012 Jun 6;15(6):927   [PMID:  22866335 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A review of the effectiveness of antidepressant medications for depressed nursing home residents.
Next Document:  ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase.