NR AWQF
AU Watts,J.C.; Drisaldi,B.; Yang,J.; Strome,B.; Horne,P.; Fraser,P.E.; Mount,H.T.J.; Schmitt-Ulms,G.
TI The novel CNS protein shadoo and PrPc share functional homology
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-35
PT Konferenz-Vortrag
AB The mammalian prion protein family currently consists of two proteins: the cellular prion protein PrPc which is expressed in the central nervous system, and Doppel (Dpl), a molecule with a similar threedimensional structure expressed in the testis. Although the function of PrPc has remained enigmatic, it is known to be protective in a number of experimental paradigms. In particular, PrPc has a potent neuroprotective effect against the toxicity of CNS-expressed Dpl and mutant forms of PrP (delta-PrP). These studies have facilitated mapping of activity determinants in PrPc and implicated the action of a cryptic PrP-like protein "pi". Here we demonstrate that mammalian SPRN, a notional third member of the PrP gene family, encodes a GPI-anchored neuronal glycoprotein termed Shadoo. Shadoo undergoes endoproteolysis and somatodendritic sorting events reminiscent of PrPc and is expressed in the brain from early postnatal life. While Shadoo and PrPc have overlaps in expression, within the hippocampus and cerebellum Shadoo protein is prominent in neurons or neuronal processes deficient in PrP, suggesting that Shadoo supplies a PrP-like activity to these neuroanatomic sites. Furthermore, in PrP-deficient neurons Shadoo protects against the toxic effect of Dpl expression, and this effect is lost when Shadoo alleles lacking the main PrP homology region are utilized. We infer that the conjectural molecule and Shadoo are synonymous. It is of interest that the ancient activity domain shared by Shadoo and PrPc coincides with the conformationally plastic region of PrPc prone to misfolding to PrPsc in prion infections.
AD Westaway Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada
SP englisch
PO Italien