Presenilin 1 is involved in maturation and trafficking of N‐cadherin to the plasma membrane
Presenilin 1 is involved in maturation and trafficking of N‐cadherin to the plasma membrane
复制标题
Presenilin 1 参与 N-钙粘蛋白的成熟和向质膜的运输
DOI：
10.1002/jnr.10753
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发表时间：
2003
影响因子：
4.2
通讯作者：
S. Shimohama
中科院分区：
文献类型：
--
作者：
K. Uemura;Naoyuki Kitagawa;R. Kohno;A. Kuzuya;T. Kageyama;K. Chonabayashi;H. Shibasaki;S. Shimohama
阿尔茨海默病（AD）的一个病理特征是广泛的突触丢失。早老素1（PS1）与早发性家族性阿尔茨海默病（FAD）的发病机制有关，并定位于突触，在那里它结合N-钙粘蛋白并调节其粘附活性。为了阐明PS1/N-cadherin相互作用在突触接触中的作用，我们建立了稳定表达野生型（wt）PS1和显性阴性（D385 A）PS1的SH-SY 5 Y细胞。我们表明，在稳定表达D385 A PS1的SH-SY 5 Y细胞中，基于钙粘蛋白的细胞间接触的形成受到抑制。相反，野生型PS1细胞表现出增强的细胞-细胞接触和集落形成。D385 A细胞中细胞-细胞接触的抑制伴随着N-钙粘蛋白亚细胞定位的改变; N-钙粘蛋白主要保留在内质网（ER）中，细胞表面表达减少。我们的结论是，PS1是必要的N-钙粘蛋白从ER到质膜的有效运输。PS1介导的N-钙粘蛋白向质膜的递送对于N-钙粘蛋白发挥其生理功能是重要的，并且它可以控制细胞-细胞接触的状态。© 2003 Wiley利斯公司
One pathological characteristic of Alzheimer's disease (AD) is extensive synapse loss. Presenilin 1 (PS1) is linked to the pathogenesis of early onset familial Alzheimer's disease (FAD) and is localized at the synapse, where it binds N‐cadherin and modulates its adhesive activity. To elucidate the role of the PS1/N‐cadherin interaction in synaptic contact, we established SH‐SY5Y cells stably expressing wild‐type (wt) PS1 and dominant‐negative (D385A) PS1. We show that the formation of cadherin‐based cell–cell contact among SH‐SY5Y cells stably expressing D385A PS1 was suppressed. Conversely, wt PS1 cells exhibited enhanced cell–cell contact and colony formation. Suppression of cell–cell contact in D385A cells was accompanied by an alteration in N‐cadherin subcellular localization; N‐cadherin was retained mainly in the endoplasmic reticulum (ER) and cell surface expression was reduced. We conclude that PS1 is essential for efficient trafficking of N‐cadherin from the ER to the plasma membrane. PS1‐mediated delivery of N‐cadherin to the plasma membrane is important for N‐cadherin to exert its physiological function, and it may control the state of cell–cell contact. © 2003 Wiley‐Liss, Inc.