Figure 10
A hypothetical model showing how glycosylation inhibits the aggregation of human PrP and decreases PrP toxicity in living cells. Under normal circumstances, posttranslational modification of nascent PrP (purple unfolded PrP), including N-linked glycosylation, occurs in the ER; the modified, folded PrP (green folded PrP modified by yellow glycans) then matures in the Golgi apparatus and finally reaches the plasma membrane with the help of the GPI anchor (gray ellipse). However, N-linked glycosylation deficiency causes PrP to remain in the cytoplasm and to have stronger PK resistance and aggregation ability than mature PrP located on the plasma membrane. Glycosylation deficiency also promotes early and late apoptosis induced by PrP oligomers (red balls) and insoluble PrP aggregates (green waves) or by the metabolic consequences of this aggregation, thereby increasing PrP toxicity. Externalized phosphatidylserine is indicated by blue sticks with green balls.
