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Involvement of glypican-1 autoprocessing in scrapie infection

Lofgren, Kajsa; Cheng, Fang LU ; Fransson, Lars-Åke LU ; Bedecs, Katarina and Mani, Katrin LU (2008) In European Journal of Neuroscience 28(5). p.964-972
Abstract
The copper-binding cellular prion protein (PrPC) and the heparan sulphate (HS)-containing proteoglycan glypican-1 (Gpc-1) can both be attached to lipid rafts via their glycosylphosphatidylinositol anchors, and copper ions stimulate their cointernalization from the cell surface to endosomes. The prion protein controls cointernalization and delivers copper necessary for S-nitrosylation of conserved cysteines in the Gpc-1 core protein. Later, during recycling through endosomal compartments, nitric oxide can be released from the S-nitroso groups and catalyses deaminative degradation and release of the HS substituents. Here, by using confocal immunofluorescence microscopy, we show that normal PrPC and Gpc-1 colocalize inside GT1-1 cells.... (More)
The copper-binding cellular prion protein (PrPC) and the heparan sulphate (HS)-containing proteoglycan glypican-1 (Gpc-1) can both be attached to lipid rafts via their glycosylphosphatidylinositol anchors, and copper ions stimulate their cointernalization from the cell surface to endosomes. The prion protein controls cointernalization and delivers copper necessary for S-nitrosylation of conserved cysteines in the Gpc-1 core protein. Later, during recycling through endosomal compartments, nitric oxide can be released from the S-nitroso groups and catalyses deaminative degradation and release of the HS substituents. Here, by using confocal immunofluorescence microscopy, we show that normal PrPC and Gpc-1 colocalize inside GT1-1 cells. However, in scrapie-infected cells (ScGT1-1), Gpc-1 protein remained at the cell surface separate from the cellular prion protein. Scrapie infection stimulated Gpc-1 autoprocessing and the generated HS degradation products colocalized with intracellular aggregates of the disease-related scrapie prion protein isoform (PrPSc). Coimmunoprecipitation experiments demonstrated an association between Gpc-1 and PrPC in uninfected cells, and between HS degradation products and PrPSc in infected cells. Silencing of Gpc-1 expression or prevention of Gpc-1 autoprocessing elevated the levels of intracellular PrPSc aggregates in infected cells. These results suggest a role for Gpc-1 autoprocessing in the clearance of PrPSc from infected cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prion, heparan sulphate, nitric oxide, proteoglycan, recycling
in
European Journal of Neuroscience
volume
28
issue
5
pages
964 - 972
publisher
Wiley-Blackwell
external identifiers
  • wos:000258729200013
  • scopus:50449094977
ISSN
1460-9568
DOI
10.1111/j.1460-9568.2008.06386.x
language
English
LU publication?
yes
id
76c2a39c-d38f-442c-9b14-dca734bc7962 (old id 1249411)
date added to LUP
2008-11-07 10:56:49
date last changed
2017-01-01 04:54:46
@article{76c2a39c-d38f-442c-9b14-dca734bc7962,
  abstract     = {The copper-binding cellular prion protein (PrPC) and the heparan sulphate (HS)-containing proteoglycan glypican-1 (Gpc-1) can both be attached to lipid rafts via their glycosylphosphatidylinositol anchors, and copper ions stimulate their cointernalization from the cell surface to endosomes. The prion protein controls cointernalization and delivers copper necessary for S-nitrosylation of conserved cysteines in the Gpc-1 core protein. Later, during recycling through endosomal compartments, nitric oxide can be released from the S-nitroso groups and catalyses deaminative degradation and release of the HS substituents. Here, by using confocal immunofluorescence microscopy, we show that normal PrPC and Gpc-1 colocalize inside GT1-1 cells. However, in scrapie-infected cells (ScGT1-1), Gpc-1 protein remained at the cell surface separate from the cellular prion protein. Scrapie infection stimulated Gpc-1 autoprocessing and the generated HS degradation products colocalized with intracellular aggregates of the disease-related scrapie prion protein isoform (PrPSc). Coimmunoprecipitation experiments demonstrated an association between Gpc-1 and PrPC in uninfected cells, and between HS degradation products and PrPSc in infected cells. Silencing of Gpc-1 expression or prevention of Gpc-1 autoprocessing elevated the levels of intracellular PrPSc aggregates in infected cells. These results suggest a role for Gpc-1 autoprocessing in the clearance of PrPSc from infected cells.},
  author       = {Lofgren, Kajsa and Cheng, Fang and Fransson, Lars-Åke and Bedecs, Katarina and Mani, Katrin},
  issn         = {1460-9568},
  keyword      = {prion,heparan sulphate,nitric oxide,proteoglycan,recycling},
  language     = {eng},
  number       = {5},
  pages        = {964--972},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Involvement of glypican-1 autoprocessing in scrapie infection},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.2008.06386.x},
  volume       = {28},
  year         = {2008},
}