The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections
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Joel C Watts [1] ; Bettina Drisaldi [1] ; Vivian Ng [1] ; Jing Yang [1] ; Bob Strome [1] ; Patrick Horne [1] ; Man-Sun Sy [2] ; Larry Yoong [1] ; Rebecca Young [3] ; Peter Mastrangelo [1] ; Catherine Bergeron [1] ; Paul E Fraser [1] ; George A Carlson [3] ; Howard T J Mount [1] ; Gerold Schmitt-Ulms [1] ; David Westaway [1]
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[1] University of Toronto
University of Toronto
Canadá
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[2] Case Western Reserve University
Case Western Reserve University
City of Cleveland, Estados Unidos
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[3] McLaughlin Research Institute
McLaughlin Research Institute
Estados Unidos
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- Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 26, Nº. 17, 2007, págs. 4038-4050
- Idioma: inglés
- Enlaces
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Resumen
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 (‘ΔPrP'). This paradigm has facilitated mapping of activity determinants in PrPC and implicated a cryptic PrPC-like protein, ‘π'. 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 ΔPrP. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for π, 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.
