N-cadherin-based adhesion enhances Abeta release and decreases Abeta42/40 ratio.
N-cadherin-based adhesion enhances Abeta release and decreases Abeta42/40 ratio.
复制标题
基于 N-钙粘蛋白的粘附增强 Abeta 释放并降低 Abeta42/40 比率。
DOI：
10.1111/j.1471-4159.2008.05760.x
复制
发表时间：
2009
影响因子：
4.7
通讯作者：
Kinoshita,A
中科院分区：
文献类型：
--
作者：
Uemura,Kengo;Lill,ChristinaM;Banks,Mary;Asada,Megumi;Aoyagi,Nobuhisa;Ando,Koichi;Kubota,Masakazu;Kihara,Takeshi;Nishimoto,Takaaki;Sugimoto,Hachiro;Takahashi,Ryosuke;Hyman,BradleyT;Shimohama,Shun;Berezovska,Oksana;Kinoshita,A
在神经元中，早老素1(PS1)/γ -分泌酶位于突触，与N -钙粘蛋白结合。我们之前报道过N -钙粘蛋白介导的细胞-细胞接触促进了PS1/γ -分泌酶的细胞表面表达。我们假设N -钙粘蛋白介导的PS1转运可能影响突触PS1 -淀粉样蛋白前体蛋白相互作用和Aβ的产生。在本报告中，我们评估了基于N -钙粘蛋白的接触对Aβ产生的影响。我们发现，在表达瑞典型人淀粉样蛋白前体细胞的中国仓鼠卵巢细胞中，稳定表达N‐cadherin可导致培养基中Aβ分泌增加。此外，N‐cadherin的表达降低了a - β42/40比值。荧光寿命成像技术显示，N‐cadherin表达对a β产生的影响伴随着PS1/γ‐分泌酶对淀粉样蛋白前体蛋白的可及性增强以及PS1的构象变化。这些结果表明，N‐cadherin介导的突触粘附可能通过PS1/N‐cadherin相互作用调节Aβ分泌和Aβ42/40比值。
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 Aβ42/40ratio. 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 Aβ42/40ratio via PS1/N‐cadherin interactions.