The CNS glycoprotein Shadoo has PrP(C)-like protective properties and displays reduced levels in prion infections.
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 ('DeltaPrP'). This paradigm has facilitated mapping of activity determinants in PrP(C) and implicated a cryptic PrP(C)-like protein, 'pi'. 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 DeltaPrP. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for pi, 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.
Watts
Joel C
JC
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
Drisaldi
Bettina
B
Ng
Vivian
V
Yang
Jing
J
Strome
Bob
B
Horne
Patrick
P
Sy
Man-Sun
MS
Yoong
Larry
L
Young
Rebecca
R
Mastrangelo
Peter
P
Bergeron
Catherine
C
Fraser
Paul E
PE
Carlson
George A
GA
Mount
Howard T J
HT
Schmitt-Ulms
Gerold
G
Westaway
David
D
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000378:metabolism; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D011485:Protein Binding
D058851:GPI-Linked Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D011328:Prions; C122036:Prnd protein, mouse; C523856:Sprn protein, mouse
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