| First Author | Hu C | Year | 2015 |
| Journal | J Neurochem | PubMed ID | 26717550 |
| Mgi Jnum | J:233614 | Mgi Id | MGI:5787714 |
| Doi | 10.1111/jnc.13518 | Citation | Hu C, et al. (2015) Nicastrin is required for APP but not Notch processing, while Aph-1 is dispensable for processing of both APP and Notch. J Neurochem |
| abstractText | The gamma-secretase complex is composed of at least four components: presenilin (PS1 or PS2), nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2 (pen-2). In this study, using knockout cell lines, our data demonstrated that knockout of NCT, as well as knockout of Pen-2, completely blocked gamma-secretase-catalyzed processing of CTFalpha and CTFbeta, the C-terminal fragments of beta-amyloid precursor protein (APP) produced by alpha-secretase and beta-secretase cleavages, respectively. Interestingly, in Aph-1-knockout cells CTFalpha and CTFbeta were still processed by gamma-secretase, indicating Aph-1 is dispensable for APP processing. Furthermore, our results indicate that Aph-1 as well as NCT is not absolutely required for Notch processing, suggesting that NCT is differentially required for APP and Notch processing. In addition, our data revealed that components of the gamma-secretase complex are also important for proteasome- and lysosome-dependent degradation of APP and that endogenous APP is mostly degraded by lysosome while exogenous APP is mainly degraded by proteasome. This article is protected by copyright. All rights reserved. |
