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  • The EMBO Journal (2007) 26, 4038 - 4050
  • doi:10.1038/sj.emboj.7601830

Published online: 16 August 2007

The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infectionsEMBO Open

Joel C Watts1,2, Bettina Drisaldi1, Vivian Ng1, Jing Yang1, Bob Strome1, Patrick Horne1, Man-Sun Sy3, Larry Yoong1, Rebecca Young4, Peter Mastrangelo1, Catherine Bergeron1,2, Paul E Fraser1,5, George A Carlson4, Howard TJ Mount1,6, Gerold Schmitt-Ulms1,2 and David Westaway1,2,7

  1. Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada
  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
  3. Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
  4. McLaughlin Research Institute, Great Falls, MT, USA
  5. Department of Medical Biophysics, University of Toronto, Toronto, Canada
  6. Department of Medicine, University of Toronto, Toronto, Canada
  7. Centre for Prions and Protein Folding Diseases, University of Alberta, Alberta, Canada

Correspondence to:

David Westaway, Centre for Prions and Protein Folding Diseases, University of Alberta, Room 116, Environmental Engineering Building, Edmonton, Alberta, Canada T6G 2M8. Tel.: +780 492 9377; Fax: +780 492 9352; E-mail: david.westaway@ualberta.ca

Received 6 March 2007; Accepted 24 July 2007

The cellular prion protein, PrPC, is neuroprotective in a number of settings and in particular prevents cerebellar degeneration mediated by CNS-expressed Doppel or internally deleted PrP ('DeltaPrP'). This paradigm has facilitated mapping of activity determinants in PrPC and implicated a cryptic PrPC-like protein, 'pi'. Shadoo (Sho) is a hypothetical GPI-anchored protein encoded by the Sprn gene, exhibiting homology and domain organization similar to the N-terminus of PrP. Here we demonstrate Sprn expression and Sho protein in the adult CNS. Sho expression overlaps PrPC, but is low in cerebellar granular neurons (CGNs) containing PrPC and high in PrPC-deficient dendritic processes. In Prnp0/0 CGNs, Sho transgenes were PrPC-like in their ability to counteract neurotoxic effects of either Doppel or DeltaPrP. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for pi, and since it engenders a PrPC-like neuroprotective activity, compromised neuroprotective activity resulting from reduced levels may exacerbate damage in prion infections. Sho may prove useful in deciphering several unresolved facets of prion biology.

  • Keywords:

    • neuroprotection,
    • prions,
    • PrP,
    • scrapie

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The EMBO Journal is published by Nature Publishing Group on behalf of European Molecular Biology Organization