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The CNS glycoprotein Shadoo has PrP C ‐like protective properties and displays reduced levels in prion infections
Author(s) -
Watts Joel C,
Drisaldi Bettina,
Ng Vivian,
Yang Jing,
Strome Bob,
Horne Patrick,
Sy ManSun,
Yoong Larry,
Young Rebecca,
Mastrangelo Peter,
Bergeron Catherine,
Fraser Paul E,
Carlson George A,
Mount Howard TJ,
SchmittUlms Gerold,
Westaway David
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601830
Subject(s) - biology , glycoprotein , p glycoprotein , virology , membrane glycoproteins , prion protein , immunology , microbiology and biotechnology , disease , medicine , drug resistance , multiple drug resistance
The cellular prion protein, PrP C , 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 PrP C and implicated a cryptic PrP C ‐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 PrP C , but is low in cerebellar granular neurons (CGNs) containing PrP C and high in PrP C ‐deficient dendritic processes. In Prnp 0/0 CGNs, Sho transgenes were PrP C ‐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 PrP C ‐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.