X11α and x11β interact with presenilin-1 via their PDZ domains

被引：88

作者：

Lau, KF

McLoughlin, DM

Standen, C

Miller, CCJ

机构：

[1] Inst Psychiat, Dept Neurosci, London SE5 8AF, England

[2] Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2000年 / 16卷 / 05期

基金：

英国惠康基金;

关键词：

D O I：

10.1006/mcne.2000.0898

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

X11 alpha and X11 beta are two neuronal adaptor proteins that interact with the Alzheimer's disease amyloid precursor protein (APP). X11 alpha and X11 beta stabilise APP and inhibit production of proteolytic APP fragments including the AP peptide that is deposited in the brains of Alzheimer's disease patients. The mechanisms by which X11 alpha and X11 beta modulate APP processing are not clear but one possibility is that they influence the activity of the secretases that cleave APP to give rise to A beta. Presenilin-1 is required for gamma -secretase activity and here we demonstrate that both X11 alpha and X11 beta interact with presenilin-1. X11/presenilin-1 binding is via two X11 PDZ domains and sequences within the carboxy-terminus of presenilin-1. We also demonstrate that both X11 alpha and X11 beta mediate the formation of complexes between APP and presenilin-1. These results suggest that the X11 regulation of APP processing is controlled, at least in part, via their interactions with APP and presenilin-1.

引用

收藏

页码：557 / 565

页数：9

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