FIGURE 9.

Model for modulation of γ-secretase complex assembly by Syvn-mediated by Rer1 degradation. NCT is incorporated into the γ-secretase complex in the ER and glycosylated in the Golgi, thereby activating γ-secretase activity (left panel). In contrast, an unassembled NCT in the Golgi is translocated to the ER by Rer1 (right panel). Rer1 is also a limiting factor that negatively regulates γ-secretase complex assembly by binding to NCT, which competes with Aph-1 (bottom panel). Syvn is involved in the degradation of Rer1, thereby facilitating the formation of the γ-secretase complex and generation of Aβ (bottom panel).