Open Access
Article
Biological properties of the PrP-like Shadoo protein
Nathalie Daude1,David Westaway1
1
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada
DOI: 10.2741/3801 Volume 16 Issue 4, pp.1505-1516
Published: 01 January 2011
(This article belongs to the Special Issue Cellular prion protein partners and signaling)
Abstract

The SPRN gene encodes the Shadoo glycoprotein (Sho), a central nervous system-expressed member of the prion protein superfamily. Sho has similarity to two features within PrPC's natively unstructured N-terminus, a hydrophobic domain and tandem repeats with positively charged residues. Indeed, scrutiny of Sho's biochemical properties in uninfected cells has revealed overlaps with the properties of PrPC, these including shared protein binding partners. SPRN is conserved in mammals, as is the prion gene PRNP, but in sheep SPRN and PRNP are both marked by polymorphic variation, suggestive of a shared selection pressure within these scrapie disease-prone livestock animals. In rodent models of prion disease there are reduced levels of Sho in infected tissues, defining a form of cross-regulation between full-length Sho holoprotein and PrPSc. In human prion disease an SPRN signal peptide polymorphism is associated with risk for sporadic Creutzfeldt-Jakob Disease (CJD), while two patients with early-onset variant CJD carried putatively inactive SPRN alleles. Further investigation of Sho as a novel tracer or modifier for the accumulation of pathologic forms of PrP may prove advantageous.

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Nathalie Daude, David Westaway. Biological properties of the PrP-like Shadoo protein. Frontiers in Bioscience-Landmark. 2011. 16(4); 1505-1516.