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PMID: 17703189 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The CNS glycoprotein Shadoo has PrP(C)-like protective properties and displays reduced levels in prion infections.

The EMBO journal ·Vol. 26 ·No. 17 ·2007-09-05 ·Pages 4038-50

Watts JC, Drisaldi B, Ng V, Yang J, Strome B, Horne P, Sy MS, Yoong L, Young R, Mastrangelo P, Bergeron C, Fraser PE, Carlson GA, Mount HT, Schmitt-Ulms G, Westaway D

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Brain/metabolism Cell Line, Tumor Cerebellum/metabolism GPI-Linked Proteins Glycoproteins/genetics,physiology Hippocampus/metabolism Mice Molecular Sequence Data Nerve Tissue Proteins/genetics,metabolism Neurons/metabolism PrPC Proteins/metabolism Prion Diseases/metabolism Prions/metabolism Protein Binding
Chemicals
GPI-Linked Proteins Glycoproteins Nerve Tissue Proteins PrPC Proteins Prions Prnd protein, mouse Sprn protein, mouse
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Watts Joel C
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
Drisaldi Bettina
Ng Vivian
Yang Jing
Strome Bob
Horne Patrick
Sy Man-Sun
Yoong Larry
Young Rebecca
Mastrangelo Peter
Bergeron Catherine
Fraser Paul E
Carlson George A
Mount Howard T J
Schmitt-Ulms Gerold
Westaway David
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601830
Published
2007-09-05
Epub
2007-00-16
Pages
4038-50
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1950727
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601830 PMC Full Text View journal details
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