The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein

被引:47
作者
Chen, TY [1 ]
Liu, PH [1 ]
Ruan, CT [1 ]
Chiu, L [1 ]
Kung, FL [1 ]
机构
[1] Natl Taiwan Univ, Sch Pharm, Taipei 10051, Taiwan
关键词
lipid rafts; Alzheimer's disease; AICD (APP intracellular domain); flotillin;
D O I
10.1016/j.bbrc.2006.01.156
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 (A beta) is a pathological hallmark of Alzheimer's disease (AD). It is derived from the amyloid precursor protein (APP) by two sequential proteolytic cleavages, which also generate the APP intracellular domain (AICD). The precise cellular function(s) of AICD still remain obscure. To elucidate the roles of AICD in the development of AD, a yeast two-hybrid system was used to screen a human brain cDNA library for proteins interacting directly with AICD. One of the potential AICD-interacting proteins identified from our screening result is a lipid raft-associated protein, flotillin-1. The interaction was confirmed by glutathione S-transferase pull-down and coimmunoprecipitation studies. Since lipid raft has been suggested to play an important role in signal transduction as well as the pathogenic development of neurodegenerative diseases, it is proposed that flotillin-1 may recruit APP to lipid rafts and therefore participate in the localization and processing of APP. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:266 / 272
页数:7
相关论文
共 42 条
[1]   Neuronal membrane cholesterol loss enhances amyloid pepticle generation [J].
Abad-Rodriguez, J ;
Ledesma, MD ;
Craessaerts, K ;
Perga, S ;
Medina, M ;
Delacourte, A ;
Dingwall, C ;
De Strooper, B ;
Dotti, CG .
JOURNAL OF CELL BIOLOGY, 2004, 167 (05) :953-960
[2]  
ALLINQUANT B, 1994, J NEUROSCI, V14, P6842
[3]   Cell biology - A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains [J].
Anderson, RGW ;
Jacobson, K .
SCIENCE, 2002, 296 (5574) :1821-1825
[4]   The caveolae membrane system [J].
Anderson, RGW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :199-225
[5]   Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins [J].
Bickel, PE ;
Scherer, PE ;
Schnitzer, JE ;
Oh, P ;
Lisanti, MP ;
Lodish, HF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13793-13802
[6]  
Borg JP, 1996, MOL CELL BIOL, V16, P6229
[7]   Axonal amyloid precursor protein expressed by neurons in vitro is present in a membrane fraction with caveolae-like properties [J].
Bouillot, C ;
Prochiantz, A ;
Rougon, G ;
Allinquant, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7640-7644
[8]   Functions of lipid rafts in biological membranes [J].
Brown, DA ;
London, E .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :111-136
[9]   Cholesterol in Alzheimer's disease and tauopathy [J].
Burns, M ;
Duff, K .
ALZHEIMER'S DISEASE: VASCULAR ETIOLOGY AND PATHOLOGY, 2002, 977 :367-375
[10]   A transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60 [J].
Cao, XW ;
Südhof, TC .
SCIENCE, 2001, 293 (5527) :115-120