Direct visualization of the gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein: association with Fe65 and translocation to the nucleus

被引：80

作者：

Kinoshita, A ^{[1
]}

Whelan, CM ^{[1
]}

Smith, CJ ^{[1
]}

Berezovska, O ^{[1
]}

Hyman, BT ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Unit,Alzheimer Dis Res Lab, Charlestown, MA 02129 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2002年 / 82卷 / 04期

关键词：

adapter protein; amyloid precursor protein; Fe65; FRET; gamma cleavage; intracellular domain;

D O I：

10.1046/j.1471-4159.2002.01016.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Amyloid-beta, the peptide that deposits as senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by a gamma secretase-mediated intramembranous cleavage. In addition to amyloid-beta, this cleavage produces a carboxyl-terminal intracellular fragment which has an unknown function. The carboxyl-terminal domain of APP interacts in the cytoplasm with an adapter protein, Fe65. We demonstrate by laser scanning confocal microscopy that a gamma secretase generated APP carboxyl-terminal domain, tagged with green fluorescent protein (GFP), translocates to the nucleus in a manner dependent upon stabilization by the adapter protein Fe65; APP which has been mutated to block interactions with Fe65 cannot be detected in the nucleus. The APP-CT domain continues to interact with Fe65 in the nucleus, as determined by both colocalization and fluorescence resonance energy transfer (FRET). Visualization of the APP-CT-Fe65 complex in the nucleus may serve as a readout for processes that modify gamma secretase release of APP-CT.

引用

页码：839 / 847

页数：9

共 35 条

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