Document Detail

Glypican-1 facilitates prion conversion in lipid rafts.
MedLine Citation:
PMID:  20681952     Owner:  NLM     Status:  In-Data-Review    
J. Neurochem. (2011) 116, 721-725. ABSTRACT: The conformational conversion of the cellular prion protein (PrP(C) ) to the infectious form (PrP(Sc) ) is the critical step in the pathogenesis of prion diseases such as Creutzfeldt-Jakob disease in humans and scrapie in sheep. Cholesterol-rich lipid rafts play a key role in the conversion of PrP(C) to PrP(Sc) and other cellular components have been identified as important cofactors to trigger, enhance, or accelerate prion formation. Amongst these heparan sulphate proteoglycans (HSPGs) and their glycosaminoglycan side-chains have been implicated in prion metabolism. Recently, the cell-surface HSPG glypican-1 was demonstrated to co-localise with PrP(C) on the cell surface and to promote its association with lipid rafts. Both PrP(C) and PrP(Sc) co-immunoprecipitated with glypican-1 and the interaction was dependent on the glycosaminoglycan side chains of glypican-1. Critically, depletion of glypican-1 in scrapie-infected N2a cells reduced the formation of PrP(Sc) , indicating that this HSPG is involved in prion formation. Further work is required to understand the molecular and cellular mechanisms underpinning the role of glypican-1 and possibly other members of the glypican family in prion metabolism, and to determine whether glypican-1 facilitates PrP(Sc) formation in vivo.
Nigel M Hooper
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  116     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  721-5     Citation Subset:  IM    
Copyright Information:
© 2011 The Author. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
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