Watt, NT, Taylor, DR, Kerrigan, TL et al. (4 more authors) (2012) Prion protein facilitates uptake of zinc into neuronal cells. Nature Communications, 3. 1134. ISSN 2041-1723
Abstract
Zinc is released into the synaptic cleft upon exocytotic stimuli, although the mechanism for its reuptake into neurons is unresolved. Here we show that the cellular prion protein enhances the uptake of zinc into neuronal cells. This prion-protein-mediated zinc influx requires the octapeptide repeats and amino-terminal polybasic region in the prion protein, but not its endocytosis. Selective antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors block the prion protein-mediated zinc uptake, and the prion protein co-immunoprecipitates with both GluA1 and GluA2 AMPA receptor subunits. Zinc-sensitive intracellular tyrosine phosphatase activity is decreased in cells expressing prion protein and increased in the brains of prion-protein-null mice, providing evidence of a physiological consequence of this process. Prion protein-mediated zinc uptake is ablated in cells expressing familial associated mutants of the protein and in prion-infected cells. These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012, Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution-Non Commercial No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Sep 2019 14:27 |
Last Modified: | 09 Sep 2019 14:27 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/ncomms2135 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134113 |
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