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Prion protein facilitates uptake of zinc into neuronal cells

Author

Listed:
  • Nicole T. Watt

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

  • David R. Taylor

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

  • Talitha L. Kerrigan

    (Leeds Institute of Genetics, Health and Therapeutics, University of Leeds
    Present address: Faculty of Medicine and Dentistry, Henry Wellcome LINE and MRC Centre for Synaptic Plasticity, University of Bristol, Bristol BS1 3NY, UK.)

  • Heledd H. Griffiths

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

  • Jo V. Rushworth

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

  • Isobel J. Whitehouse

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

  • Nigel M. Hooper

    (Faculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds)

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.

Suggested Citation

  • Nicole T. Watt & David R. Taylor & Talitha L. Kerrigan & Heledd H. Griffiths & Jo V. Rushworth & Isobel J. Whitehouse & Nigel M. Hooper, 2012. "Prion protein facilitates uptake of zinc into neuronal cells," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2135
    DOI: 10.1038/ncomms2135
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    Cited by:

    1. Mohadeseh Mehrabian & Dylan Brethour & Declan Williams & Hansen Wang & Hélène Arnould & Benoit Schneider & Gerold Schmitt-Ulms, 2016. "Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-27, June.

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