Abstract
γ-secretase is a protease complex with at least four components: presenilin, nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2 (Pen-2). In this study, using knockout cell lines and small interfering RNA technology, our data demonstrated that the disappeared presenilin 1 C-terminal fragment (PS1C) caused by knockdown of pen-2 or knockout of NCT or Aph-1 was recovered by the addition of proteasome inhibitors, indicating that Pen-2, as well as NCT and Aph-1α, is dispensable for presenilin endoproteolysis. Our data also demonstrate that the formation of the nicastrin-Aph-1 subcomplex plays not only an important role in γ-secretase complex assembly but also in recruiting substrate C-terminal fragment of amyloid precursor protein generated by β-cleavage. Ablating any one component resulted in the instability of other components of the γ-secretase complex, and the presence of all three of the other components is required for full maturation of NCT.
Original language | English (US) |
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Pages (from-to) | 837-844 |
Number of pages | 8 |
Journal | Journal of Neurochemistry |
Volume | 123 |
Issue number | 5 |
DOIs | |
State | Published - Dec 2012 |
Keywords
- APP
- Alzheimer's disease
- gamma-secretase
- pen-2
- presenilin
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience