NR AWJD
AU Löfgren,K.M.; Cheng,F.; Fransson,L.A.; Mani,K.; Bedecs,K.
TI The involvement of glyican-1 in prion formation
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-24
PT Konferenz-Poster
AB Conversion of the cellular prion protein (PrPc) to the disease-causing isoform (PrPsc) may occur during endocytosis and/or recycling of PrPc. The requirement of cellular cofactors involved in the conversion process has been suggested. Several lines of evidence have shown sulfated glycosaminoglycans like heparan sulfate (HS), heparin and pentosan sulfate to affect the metabolism of prions, and a cellular heparan sulfate has been shown to participate in prion propagation in scrapie-infected cells. Additionally, HS accumulates in prion amyloid plaques. Since PrPc binds to HS and heparin, it has been proposed that sulfated glycans inhibits PrPsc formation by competing with the binding of PrPc to a putative cellular HS proteoglycan. However, which HS proteoglycan is involved in PrPsc formation remains to be determined. One candidate is the glycosylphosphatidylinositol-anchored, raft-resident glypican-1 (Gpc-1) which is particularly expressed in the adult brain. During recycling of Gpc-1, degradation of HS takes place. Recently, the metabolism of glycosaminoglycans was shown to be impaired in prion disease. Correspondingly, in this study, we show that the localization and processing of recycling Gpc-1 is dramatically altered in GT1-1 cells which have been prion-infected (ScGT1). Confocal laser scanning immunofluorescence microscopy shows that in ScGT1 cells, Gpc-1 assumes a punctuate distribution, in contrast to the even distribution in uninfected cells. Additionally, NO-catalyzed Gpc-1 HS degradation is increased, whereas enzymatic heparanase-dependent HS cleavage is decreased in ScGT1 cells. Our preliminary results have raised the hypothesis that Gpc-1 might be serving as a receptor for cellular uptake of prions, and/or as a cofactor for PrPc to PrPsc conversion.
AD K. Löfgren, K. Bedecs: Department of Biochemistry and Biophysics, Division of Biochemistry, Stockholm University, SE-106 91, Stockholm, Sweden; F. Cheng, L-Å. Fransson, K. Mani: Department of Experimental Medical Science, Division of Neuroscience, Biomedical Center C13, SE-221 84, Lund University, Lund, Sweden
SP englisch
PO Italien