919 membrane, PrPC can be induced to convert to the protease-resistant state by PrPSc in the same membrane but resists conversion by PrPSc in separate membranes. This suggests that interactions between PrPC and PrPSc occur through molecular surfaces held close to the membrane by the GPI anchor (see the figure)(Gerald Baron, Rocky Mountain Laboratories). When bound to membrane lipid rafts in the GPI-independent mode, PrPC can be converted by exogenous PrPSc and can also undergo spontaneous conformational changes and aggregations (Teresa Pinheiro, University of Warwick). Finally, studies of PrP trafficking demonstrated that PrPC can rapidly exit its raft membrane environment and enter coated pits during endocytosis, further suggesting that different membrane environments might influence the ability of PrPC to form PrPSc (Angela Jen, King’s College London).

At the meeting, a consensus emerged that truncated forms of PrPSc and alternatively processed forms of PrPC may be important in TSE pathogenesis. Truncated forms of PrPSc derived from full-length PrPSc found in the human TSE disease, Gerstmann-Straussler-Scheinker syndrome (GSS), may provide clues to how the protease-resistant core of PrPSc is formed (Pierluigi Gambetti, Case Western Reserve University). These truncated PrP molecules may be the result of strain-and species-specific conformational differences in PrPSc that are influenced by the amino-terminal portion of PrPC (Bruce Chesebro, Rocky Mountain Laboratories).