Prion protein glycosylation is not required for strain-specific neurotropism.
In this study, we tested the hypothesis that the glycosylation of the pathogenic isoform of the prion protein (PrP(Sc)) might encode the selective neurotropism of prion strains. We prepared unglycosylated cellular prion protein (PrP(C)) substrate molecules from normal mouse brain by treatment with PNGase F and used reconstituted serial protein cyclic misfolding amplification reactions to produce RML and 301C mouse prions containing unglycosylated PrP(Sc) molecules. Both RML- and 301C-derived prions containing unglycosylated PrP(Sc) molecules were infectious to wild-type mice, and neuropathological analysis showed that mice inoculated with these samples maintained strain-specific patterns of PrP(Sc) deposition and neuronal vacuolation. These results show that PrP(Sc) glycosylation is not necessary for strain-dependent prion neurotropism.
Piro
Justin R
JR
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Harris
Brent T
BT
Nishina
Koren
K
Soto
Claudio
C
Morales
Rodrigo
R
Rees
Judy R
JR
Supattapone
Surachai
S
D000818:Animals; D006031:Glycosylation; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D011328:Prions / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013379:Substrate Specificity
D011328:Prions