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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1249411
- author
- Lofgren, Kajsa
; Cheng, Fang
LU
; Fransson, Lars-Åke
LU
; Bedecs, Katarina
and Mani, Katrin
LU
- organization
- publishing date
- 2008
- 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
- 2016-04-01 12:10:41
- date last changed
- 2023-09-01 22:16:20
@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}},
keywords = {{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}},
doi = {{10.1111/j.1460-9568.2008.06386.x}},
volume = {{28}},
year = {{2008}},
}