title: Selective neuronal targeting in prion disease.
abstract: The pattern of scrapie prion protein (PrP(Sc)) accumulation in the brain is different for each prion strain. We tested whether the PrP(Sc) deposition pattern is influenced by the Asn-linked oligosaccharides of PrP(C) in transgenic mice. Deletion of the first oligosaccharide altered PrP(C) trafficking and prevented infection with two prion strains. Deletion of the second did not alter PrP(C) trafficking, permitted infection with one prion strain, and had a profound effect on the PrP(Sc) deposition pattern. Our data raise the possibility that glycosylation can modify the conformation of PrP(C). Glycosylation could affect the affinity of PrP(C) for a particular conformer of PrP(Sc), thereby determining the rate of nascent PrP(Sc) formation and the specific patterns of PrP(Sc) deposition.
authors.affiliation: Department of Pathology, University of California, San Francisco 94143, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: H
authors.initials: H
authors.lastname: Sánchez
authors.forename: F
authors.initials: F
authors.lastname: Yehiely
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.forename: A
authors.initials: A
authors.lastname: Ninchak-Casey
authors.forename: V
authors.initials: V
authors.lastname: Daggett
authors.forename: A P
authors.initials: AP
authors.lastname: Camerino
authors.forename: J
authors.initials: J
authors.lastname: Cayetano
authors.forename: M
authors.initials: M
authors.lastname: Rogers
authors.forename: D
authors.initials: D
authors.lastname: Groth
authors.forename: M
authors.initials: M
authors.lastname: Torchia
authors.forename: P
authors.initials: P
authors.lastname: Tremblay
authors.forename: M R
authors.initials: MR
authors.lastname: Scott
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009844:Oligosaccharides / Q000378:metabolism; D016366:Open Reading Frames; D009928:Organ Specificity; D018621:PrPC Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion
chemical_list: D009844:Oligosaccharides; D018621:PrPC Proteins