Résumé
The central pathogenic event in prion diseases is the posttranslational conversion of PrPC, a normal cell-surface glycoprotein, into PrPSc, the principal constituent of infectious prion particles (reviewed by Prusiner, 1996). This transformation, which is hypothesized result from a change in the conformation of the polypeptide chain, has been studied both in vivo using transgenic mice (Scott et al., 1996) and in vitro using purified proteins and synthetic peptides (Bessen et al., 1995; Kaneko et al., 1995). The approach we have chosen to take is a cell biological one, focusing on the biosynthesis, posttranslational processing, and cellular trafficking of PrPC and PrPSc in cultured cells (Harris et al., 1996). The techniques we employ include metabolic labeling, immunochemical analysis, microscopy, and subcellular fractionation. The primary advantage of a cell biological approach is the ability to study the formation of PrPSc in the context of the membranes, organelles, and cellular cofactors that are likely to be important in mediating the conversion process.