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The glycosylphosphatidylinositol anchor is a major determinant of prion binding and replication.

Bate, C, Tayebi, M and Williams, A (2010) The glycosylphosphatidylinositol anchor is a major determinant of prion binding and replication. Biochem J, 428 (1). pp. 95-101.

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The prion diseases occur following the conversion of the cellular prion protein (PrPC) into an alternatively folded, disease-associated isoform (PrPSc). However, the spread of PrPSc from cell to cell is poorly understood. In the present manuscript we report that soluble PrPSc bound to and replicated within both GT1 neuronal cells and primary cortical neurons. The capacity of PrPSc to bind and replicate within cells was significantly reduced by enzymatic modification of its GPI (glycosylphosphatidylinositol) anchor. Thus PrPSc that had been digested with phosphatidylinositol-phospholipase C bound poorly to GT1 cells or cortical neurons and did not result in PrPSc formation in recipient cells. PrPSc that had been digested with phospholipase A2 (PrPSc-G-lyso-PI) bound readily to GT1 cells and cortical neurons but replicated less efficiently than mock-treated PrPSc. Whereas the addition of PrPSc increased cellular cholesterol levels and was predominantly found within lipid raft micro-domains, PrPSc-G-lyso-PI did not alter cholesterol levels and most of it was found outside lipid rafts. We conclude that the nature of the GPI anchor attached to PrPSc affected the binding of PrPSc to neurons, its localization to lipid rafts and its ability to convert endogenous PrPC.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Bate, C
Williams, A
Date : 15 May 2010
DOI : 10.1042/BJ20091469
Uncontrolled Keywords : Animals, Cells, Cultured, Embryo, Mammalian, Glycosylphosphatidylinositols, Mice, Mice, Knockout, Mice, Transgenic, Neurons, PrPC Proteins, PrPSc Proteins, Prions
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:09
Last Modified : 24 Jan 2020 18:36

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