title: The CNS glycoprotein Shadoo has PrP(C)-like protective properties and displays reduced levels in prion infections.
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.
authors: Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
authors: Joel C
authors: JC
authors: Watts
authors: Bettina
authors: B
authors: Drisaldi
authors: Vivian
authors: V
authors: Ng
authors: Jing
authors: J
authors: Yang
authors: Bob
authors: B
authors: Strome
authors: Patrick
authors: P
authors: Horne
authors: Man-Sun
authors: MS
authors: Sy
authors: Larry
authors: L
authors: Yoong
authors: Rebecca
authors: R
authors: Young
authors: Peter
authors: P
authors: Mastrangelo
authors: Catherine
authors: C
authors: Bergeron
authors: Paul E
authors: PE
authors: Fraser
authors: George A
authors: GA
authors: Carlson
authors: Howard T J
authors: HT
authors: Mount
authors: Gerold
authors: G
authors: Schmitt-Ulms
authors: David
authors: D
authors: Westaway
mesh_terms: 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
chemical_list: D058851:GPI-Linked Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D011328:Prions; C122036:Prnd protein, mouse; C523856:Sprn protein, mouse
references: Nature. 2001 Aug 16;412(6848):739-43
references: 11507642
references: Mol Biol Evol. 2004 Dec;21(12):2210-31
references: 15342797
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15288-93
references: 11734625
references: EMBO J. 2002 Jul 1;21(13):3317-26
references: 12093733
references: EMBO J. 2002 Jul 15;21(14):3652-8
references: 12110578
references: Mamm Genome. 2002 Dec;13(12):696-703
references: 12514748
references: Mol Cell Neurosci. 2003 May;23(1):144-55
references: 12799144
references: EMBO J. 2003 Jul 15;22(14):3591-601
references: 12853474
references: Gene. 2003 Sep 18;314:89-102
references: 14527721
references: Science. 2004 Mar 5;303(5663):1514-6
references: 14752167
references: J Biol Chem. 2004 Mar 19;279(12):11170-8
references: 14711812
references: Cell. 1993 Jul 2;73(7):1339-47
references: 8100741
references: Protein Sci. 1992 Oct;1(10):1343-52
references: 1363897
references: Am J Pathol. 2004 Jun;164(6):2279-88
references: 15161660
references: J Biol Chem. 1995 Aug 11;270(32):19173-80
references: 7642585
references: Nature. 1996 Jan 25;379(6563):339-43
references: 8552188
references: Nature. 1996 Jul 11;382(6587):180-2
references: 8700211
references: J Physiol. 1997 Apr 1;500 ( Pt 1):1-15
references: 9097928
references: FEBS Lett. 1997 Aug 18;413(2):282-8
references: 9280298
references: J Mol Biol. 1997 Oct 31;273(3):614-22
references: 9356250
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13452-7
references: 9391046
references: J Virol. 1998 Feb;72(2):1153-9
references: 9445012
references: Cell. 1998 Apr 17;93(2):203-14
references: 9568713
references: J Mol Biol. 1999 Jun 25;289(5):1163-78
references: 10373359
references: Lab Invest. 1999 Jun;79(6):689-97
references: 10378511
references: Nature. 1999 Jul 15;400(6741):225-6
references: 10421360
references: Neurosci Lett. 2004 Nov 30;372(1-2):146-50
references: 15531106
references: J Biol Chem. 2004 Dec 31;279(53):55443-54
references: 15459186
references: Biochem Biophys Res Commun. 2005 Jul 29;333(2):448-54
references: 15950943
references: J Neurosci. 2005 Sep 28;25(39):8967-77
references: 16192387
references: Neurobiol Dis. 2005 Nov;20(2):442-9
references: 15893468
references: Biochem Biophys Res Commun. 2006 Mar 3;341(1):218-24
references: 16414019
references: Microbiol Immunol. 2006;50(3):203-9
references: 16547418
references: J Biol Chem. 2006 May 12;281(19):13828-36
references: 16554307
references: EMBO J. 2007 Jan 24;26(2):538-47
references: 17245436
references: EMBO J. 2007 Jan 24;26(2):548-58
references: 17245437
references: Brain Res. 2001 Mar 30;896(1-2):118-29
references: 11277980
references: Nature. 1999 Dec 16;402(6763):822-6
references: 10617204
references: J Biol Chem. 2000 Sep 1;275(35):26834-41
references: 10842180
references: Am J Pathol. 1986 Jan;122(1):1-5
references: 3079955
references: J Gen Virol. 1986 Feb;67 ( Pt 2):255-63
references: 3080549
references: Cell. 1986 Aug 15;46(4):503-11
references: 3015416
references: J Neuropathol Exp Neurol. 1987 Jul;46(4):461-73
references: 3598605
references: Cell. 1989 Dec 1;59(5):847-57
references: 2574076
references: Cell. 1990 Nov 16;63(4):673-86
references: 1977523
references: Nature. 1992 Apr 16;356(6370):577-82
references: 1373228
references: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7620-4
references: 1354357
references: EMBO J. 2001 Feb 15;20(4):694-702
references: 11179214
references: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2352-7
references: 11226243
references: J Biol Chem. 2001 Jun 15;276(24):21562-70
references: 11279122
references: J Mol Biol. 2000 Aug 18;301(3):567-73
references: 10966770
references: Neuron. 2000 Aug;27(2):399-408
references: 10985358
references: J Biol Chem. 2000 Nov 10;275(45):35612-6
references: 10952979
references: Neuroreport. 2001 Jan 22;12(1):179-83
references: 11201083
references: J Virol. 2004 Jun;78(12):6449-58
references: 15163738
references: Ann Neurol. 2004 Jun;55(6):781-92
references: 15174012
references: Am J Pathol. 2004 Jul;165(1):227-35
references: 15215178
references: J Biol Chem. 2004 Sep 17;279(38):39671-6
references: 15133046
references: J Biol Chem. 2001 Oct 19;276(42):39145-9
references: 11522774