Shadoo (Sho) is a neuronally expressed glycoprotein of unknown function. Although there is
no overall sequence homology to the cellular prion protein (PrP C), both proteins contain a
highly conserved internal hydrophobic domain (HD) and are tethered to the outer leaflet of
the plasma membrane via a C-terminal glycosylphosphatidylinositol anchor. A previous
study revealed that Sho can reduce toxicity of a PrP mutant devoid of the HD (PrPΔHD). We
have now studied the stress-protective activity of Sho in detail and identified domains …