Amplification of Fas-mediated apoptosis in type II cells via microdomain recruitment

被引:30
作者
Legembre, P
Daburon, S
Moreau, P
Ichas, F
de Giorgi, F
Moreau, JF
Taupin, JL
机构
[1] Univ Bordeaux 2, CNRS, UMR 5164, Lab CIRID, F-33076 Bordeaux, France
[2] Univ Bordeaux 2, CNRS, UMR 5200, Lab Biogenese Membranaire, F-33076 Bordeaux, France
[3] Ctr Lutte Canc Bergonie, F-33600 Pessac, France
[4] Inst Europeen Chim & Biol, F-33600 Pessac, France
关键词
D O I
10.1128/MCB.25.15.6811-6820.2005
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
Fas triggers apoptosis via the caspase cascade when bound to its ligand FasL. In type I cells, Fas is concentrated into the plasma membrane lipid rafts, and these domains are required for the apoptotic signal to occur. In contrast, Fas is excluded from the microdomains in type II cells. We report that the coligation with Fas of the membrane receptor CD28 strongly increases Fas-induced apoptosis in type II T lymphocytes, whereas it has no effect in a type I cell line. The effect of CD28 is independent of its intracellular region and requires the recruitment of the microdomains. Indeed, upon CD28 costimulation, Fas is redistributed in the lipid rafts, and their disruption with a cholesterol chellator abrogates the effect of CD28. The microdomain-mediated cell death amplification does not alter death-induced signaling complex formation and is mediated by the enhancement of the mitochondriall apoptotic pathway. These findings indicate that the sensitivity to Fas-induced apoptosis of type II cells can be amplified in vivo by the recruitment of lipid rafts following interactions between nonapoptotic ligand/receptor pairs during cell-to-cell contacts.
引用
收藏
页码:6811 / 6820
页数:10
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