Models. (A, a) Map of PrP^Sc metabolism and trafficking in infected cells. FL PrP^Sc is formed on rafts either on the cell surface or in an endocytic compartment. FL PrP^Sc is then N-proximally truncated into PrP27-30 by acidic proteases and accumulates in endolysosomes. (b) Strings acquire PrP^Sc either by converting cell surface PrP^C (alternative i) or by importing it from intracellular conversion compartments (ii). PrP27-30 is probably recycled from hydrolytic endosomes (dashed arrows). However, PrP27-30 could also be generated by in-string truncation on the cell surface. (c) Whereas PrP^C is rapidly endocytosed in subconfluent GT1, PrP^Sc is delayed in cell surface strings for >4 h. (B) Models of string structure. (Model A) Strings are amyloid fibrils/ribbons anchored to the cell surface. (Model B) Strings are composed of PrP^Sc foci aligned by yet unknown cellular structures (e.g., ECM or membrane elements; see Discussion).