| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Nicastrin is one of components of γ-secretase complex, catalyzes the cleavage of amyloid precursor protein to generate amyloid-β protein (Aβ). NCT becomes matured through complex glycosylation and play important role in γ-secretase activity. However, the role of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown. We investigated the effect of NCT glycosylation on γ-secretase activity and substrate specificity in a group of glycosylation mutant lectin resistant CHO (Lec) cells. CHO Lec-1 cells lack glycosyltransferase-I, thus N-glycan on NCT are all oligomannose type. We found that mutant CHO Lec-1 and Lec-2 reduced γ-secretase activity in both cell-based and biochemical assays, and that CHO Lec-1 preferentially reduced Aβ generation. Our data suggests that thorough glycosylation of NCT is critical for enzymatic activity and substrate preference of γ-secretase.
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