Dependency of γ-secretase complex activity on the structural integrity of the bilayer

被引:4
作者
Zhou, Hua [1 ]
Zhou, Shuxia [1 ]
Walian, Peter J. [1 ]
Jap, Bing K. [1 ]
机构
[1] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
Membrane protein; Aspartyl protease; Alzheimer's disease; LIPID RAFTS; INTRACELLULAR DOMAIN; INTRAMEMBRANE PROTEOLYSIS; SIGNAL-TRANSDUCTION; HUMAN BRAIN; BETA-APP; IN-VIVO; PRESENILIN; CLEAVAGE; RECONSTITUTION;
D O I
10.1016/j.bbrc.2010.10.017
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
gamma-secretase is a membrane protein complex associated with the production of All peptides that are pathogenic in Alzheimer's disease. We have characterized the activity of gamma-secretase complexes under a variety of detergent solubilization and reconstitution conditions, and the structural state of proteoliposomes by electron microscopy. We found that gamma-secretase activity is highly dependent on the physical state or integrity of the membrane bilayer - partial solubilization may increase activity while complete solubilization will abolish it. The activity of well-solubilized gamma-secretase can be restored to near native levels when properly reconstituted into a lipid bilayer environment. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:291 / 296
页数:6
相关论文
共 39 条
[1]   Presenilins and the intramembrane proteolysis of proteins: facts and fiction [J].
De Strooper, B ;
Annaert, W .
NATURE CELL BIOLOGY, 2001, 3 (10) :E221-E225
[2]   Reconstitution of γ-secretase activity [J].
Edbauer, D ;
Winkler, E ;
Regula, JT ;
Pesold, B ;
Steiner, H ;
Haass, C .
NATURE CELL BIOLOGY, 2003, 5 (05) :486-488
[3]   Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts [J].
Ehehalt, R ;
Keller, P ;
Haass, C ;
Thiele, C ;
Simons, K .
JOURNAL OF CELL BIOLOGY, 2003, 160 (01) :113-123
[4]   Biomedicine - A portrait of Alzheimer secretases - New features and familiar faces [J].
Esler, WP ;
Wolfe, MS .
SCIENCE, 2001, 293 (5534) :1449-1454
[5]   Partial purification and characterization of γ-secretase from post-mortem human brain [J].
Farmery, MR ;
Tjernberg, LO ;
Pursglove, SE ;
Bergman, A ;
Winblad, B ;
Näslund, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :24277-24284
[6]   Purification and characterization of the human γ-secretase complex [J].
Fraering, PC ;
Ye, WJ ;
Strub, JM ;
Dolios, G ;
LaVoie, MJ ;
Ostaszewski, BL ;
van Dorsselaer, A ;
Wang, R ;
Selkoe, DJ ;
Wolfe, MS .
BIOCHEMISTRY, 2004, 43 (30) :9774-9789
[7]   Rat brain γ-secretase activity is highly influenced by detergents [J].
Franberg, Jenny ;
Welander, Hedvig ;
Aoki, Mikio ;
Winblad, Bengt ;
Tjernberg, Lars O. ;
Frykman, Susanne .
BIOCHEMISTRY, 2007, 46 (25) :7647-7654
[8]   Active γ-secretase is localized to detergent-resistant membranes in human brain [J].
Hur, Ji-Yeun ;
Welander, Hedvig ;
Behbahani, Homira ;
Aoki, Mikio ;
Franberg, Jenny ;
Winblad, Bengt ;
Frykman, Susanne ;
Tjernberg, Lars O. .
FEBS JOURNAL, 2008, 275 (06) :1174-1187
[9]  
JAP BK, 2001, 2 DIMENSIONAL CRYSTA
[10]   Nectin-1α, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/γ-secretase-like cleavage [J].
Kim, DY ;
Ingano, LAM ;
Kovacs, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (51) :49976-49981