2003
DOI: 10.1242/jcs.00292
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γ-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation

Abstract: Nicastrin and presenilin are two major components of the γ-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesized in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin). These modifications are not… Show more

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Cited by 176 publications
(214 citation statements)
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“…As expected, and as reported previously (17,18), compared with vehicle-treated cells, kifunensine treatment affected neither the levels of APP-carboxylterminal fragments (CTFs) nor levels of secreted Aβ peptides (Fig. 1A, APP-CTFs and Aβ; compare lanes 3 and 4 with 5 and 6, respectively), suggesting that kifunensine-mediated inhibition of oligosaccharide maturation does not impair γ-secretase activity.…”
supporting
confidence: 89%
“…As expected, and as reported previously (17,18), compared with vehicle-treated cells, kifunensine treatment affected neither the levels of APP-carboxylterminal fragments (CTFs) nor levels of secreted Aβ peptides (Fig. 1A, APP-CTFs and Aβ; compare lanes 3 and 4 with 5 and 6, respectively), suggesting that kifunensine-mediated inhibition of oligosaccharide maturation does not impair γ-secretase activity.…”
supporting
confidence: 89%
“…In HsNCT, there are 16 potential N-glycosylation sites. The glycosylation of HsNCT is reported to be important for the formation and stabilization of the γ-secretase complex, although glycosylation may not be essential for the protease activity of γ-secretase (32,33). Consistent with this conclusion, the potential N-glycosylation sites of nicastrin are not conserved across different organisms.…”
Section: Discussionmentioning
confidence: 88%
“…Studies have shown that PEN-2 and APH-1 may be involved in coordinately regulating proteolytic processing of PS1 (34,37). Nicastrin has been shown to form a complex with PS1 (38), and its presence is required both for the cleavage of PS1 into its active C-and N-terminal fragments and for its transport beyond the ER (39,40). Likewise, in the absence of PS1, NCT is not transported suggesting that interactions between these proteins are needed for them to either fold correctly, making it possible to exit the ER, or perhaps to mask an ER retention signal (27)(28)(29).…”
Section: Discussionmentioning
confidence: 99%