NR AXYP
AU Westaway,D.; Watts,J.C.; Ng,V.; Daude,N.; Yang,J.; Horne,P.; Strome,B.; Young,R.; Carlson,G.A.; Fraser,P.E.; Schmitt-Ulms,G.
TI Biological Activities of the Shadoo Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.185
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Although the function of PrPc has remained enigmatic, it is neuroprotective in a number of paradigms. In particular, several labs have demonstrated a potent protective effect against degeneration of the cerebellum mediated by CNS-expressed Doppel or internally deleted forms of PrP ("deltaPrP"). These studies have facilitated mapping of activity determinants in PrPc and implicated the action of a cryptic PrPc-like protein termed "pi". Shadoo (Sho) is a hypothetical GPI-anchored glycoprotein encoded by the SPRN gene, exhibiting homology and domain organization similar to the N-
terminus of PrP. In situ hybridization, histology and blot analysis demonstrate the presence of Sho in the adult CNS of wt mice. Sho expression has overlaps with PrPc but is low in cerebellar granular neurons (CGNs) containing PrPc and high in PrPcdeficient dendritic processes of the hippocampus and cerebellum. In Prnp0/0 cerebellar granular neurons (CGNs), transgene-encoded wt Sho resembles wt PrPc in counteracting the toxic effect of expressing either Doppel or dPrP. This PrP-like neuroprotective activity indicates an overlap in the biology of Sho and PrPc and begs the question of Sho's activity in prion disease. Here it is notable that immunohistochemistry defines Sho in some neuroanatomical structures that become clinical target areas in experimental scrapie. Furthermore, wt mice infected with RML prions exhibit a dramatic reduction in endogenous Sho protein versus healthy controls. Our data define Sho as a bona fide neuronal protein and a plausible candidate for pi. Perhaps more importantly, loss of neuroprotective activity resulting from reduced Sho expression could contribute to clinical disease. Thus Sho comprises a new tool to explore unresolved facets of prion biology.
AD D. Westaway, J. Yang, University of Alberta; J. Watts, V. Ng, N. Daude, P. Horne, B. Strome, P.E. Fraser, G. Schmitt-Ulms, University of Toronto, Canada; R. Young, G.A. Carlson, McLaughlin Research Institute, USA
SP englisch
PO Schottland