Document Detail


Prion propagation in cells expressing PrP glycosylation mutants.
MedLine Citation:
PMID:  21248032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.
Authors:
Muhammad K Salamat; Michel Dron; Jérôme Chapuis; Christelle Langevin; Hubert Laude
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-19
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-16     Completed Date:  2011-05-13     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3077-85     Citation Subset:  IM    
Affiliation:
INRA, U892 Virologie Immunologie Moléculaires, F-78350 Jouy-en-Josas, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Membrane / chemistry
Glycosylation
Golgi Apparatus / chemistry
Mutation, Missense*
Prions / genetics,  metabolism*
Protein Processing, Post-Translational*
Protein Transport
Rabbits
Sheep
Chemical
Reg. No./Substance:
0/Prions
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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