Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype

被引：110

作者：

Yamatsuji, T

Okamoto, T

Takeda, S

Murayama, Y

Tanaka, N

Nishimoto, I

机构：

[1] HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129

[2] UNIV TOKYO,SCH MED,DEPT MED 4,BUNKYO KU,TOKYO 112,JAPAN

[3] OKAYAMA UNIV,SCH MED,DEPT SURG 1,OKAYAMA 700,JAPAN

来源：

EMBO JOURNAL | 1996年 / 15卷 / 03期

关键词：

amyloid precursor protein; apoptosis; bcl-2; familial Alzheimer's disease; G proteins;

D O I：

10.1002/j.1460-2075.1996.tb00382.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：

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V642I, V642F and V642G have been discovered in APP(695). Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation, Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP(695) had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity.

引用

页码：498 / 509

页数：12

共 58 条

[1]

BAFFY G, 1994, J BIOL CHEM, V269, P8483

[2] MULTIPLE INDEPENDENT ACTIVATIONS OF THE NEU ONCOGENE BY A POINT MUTATION ALTERING THE TRANSMEMBRANE DOMAIN OF P185 [J].