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- Title
N-cadherin-based adhesion enhances Aβ release and decreases Aβ<sub>42/40</sub> ratio.
- Authors
Uemura, Kengo; Lill, Christina M.; Banks, Mary; Asada, Megumi; Aoyagi, Nobuhisa; Ando, Koichi; Kubota, Masakazu; Kihara, Takeshi; Nishimoto, Takaaki; Sugimoto, Hachiro; Takahashi, Ryosuke; Hyman, Bradley T.; Shimohama, Shun; Berezovska, Oksana; Kinoshita, Ayae
- Abstract
In neurons, Presenilin 1(PS1)/γ-secretase is located at the synapses, bound to N-cadherin. We have previously reported that N-cadherin-mediated cell–cell contact promotes cell-surface expression of PS1/γ-secretase. We postulated that N-cadherin-mediated trafficking of PS1 might impact synaptic PS1-amyloid precursor protein interactions and Aβ generation. In the present report, we evaluate the effect of N-cadherin-based contacts on Aβ production. We demonstrate that stable expression of N-cadherin in Chinese hamster ovary cells, expressing the Swedish mutant of human amyloid precursor protein leads to enhanced secretion of Aβ in the medium. Moreover, N-cadherin expression decreased Aβ42/40 ratio. The effect of N-cadherin expression on Aβ production was accompanied by the enhanced accessibility of PS1/γ-secretase to amyloid precursor protein as well as a conformational change of PS1, as demonstrated by the fluorescence lifetime imaging technique. These results indicate that N-cadherin-mediated synaptic adhesion may modulate Aβ secretion as well as the Aβ42/40 ratio via PS1/N-cadherin interactions.
- Subjects
ADHESION; AMYLOID; NEURONS; SECRETION; SYNAPSES; ALZHEIMER'S patients; CADHERINS
- Publication
Journal of Neurochemistry, 2009, Vol 108, Issue 2, p350
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2008.05760.x