Biosynthesis of the Scrapie Prion Protein in Scrapie-Infected Cells
Compelling evidence argues that the major component of the scrapie prion is a host- encoded protein, the scrapie prion protein (PrPSc) (reviewed in Prusiner, 1991). The events of PrPSc biosynthesis are thus of central importance to understanding the biology of scrapie. PrPSc is the abnormal isoform of a normal phosphoinositol glycolipid (GPI)-anchored plasma membrane sialoglycoprotein PrPC. While the two PrP isoforms differ strikingly in many of their properties, their structural differences have not yet been elucidated. PrPSc is insoluble in detergents and possesses a protease-resistant core, while PrPC is readily soluble in most detergents and is completely degraded by proteases. In infected cells in culture, PrPSc becomes protease-resistant as a result of an as yet unidentified post-translational event (Borchelt et al., 1990) unrelated to PrP N-linked glycosylation (Taraboulos et al., 1990a). In scrapie infected cells in culture, PrPSc accumulates primarily within secondary lysosomes (Taraboulos et al., 1990b; McKinley et al., 1991). All PrP antibodies described to date react equally well with both PrPC and denatured PrPSc, but are much less reactive with native PrPSc. To study further the biosynthesis of protease-resistant PrPSc, we have used scrapie-infected ScN2a and ScHaB cells in pulse-chase radiolabeling experiments.
KeywordsScrapie Monensin Phosphoinositol
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