The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability.
The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability.
复制标题
FASL和FAS的细胞外结构域足以形成高稳定性的超分子FASL-FAS簇。
DOI：
10.1083/jcb.200501048
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发表时间：
2005-03-28
影响因子：
7.8
通讯作者：
Wajant, Harald
中科院分区：
文献类型：
--
作者：
Henkler, Frank;Behrle, Eva;Dennehy, Kevin M;Wicovsky, Andreas;Peters, Nathalie;Warnke, Clemens;Pfizenmaier, Klaus;Wajant, Harald
利用Fas和FasL的荧光突变体，我们发现膜上的FasL和Fas形成了形状灵活但仍然稳定和持久的超分子簇。在caspase-8或FADD缺失的细胞中或使用Fas的胞质缺失突变体时，膜FasL诱导的Fas簇的形成表明，Fas簇的形成不依赖于细胞质Fas信号复合体和下游激活的信号通路的组装。相反，交联的可溶性FasL不能聚集Fas的胞质缺失突变体，但仍能诱导具有信号功能的全长Fas的聚集。此外，在脂筏不稳定成分甲基-β-环糊精存在的情况下，Fas-L诱导的Fas簇形成，而可溶性Fas-L诱导的Fas聚集被阻断。综上所述，这些数据表明，Fas和FasL的胞外结构域足以驱动膜上FasL诱导的超分子Fas-FasL复合体的形成，而可溶性FasL诱导的Fas聚集依赖于脂筏和与Fas胞内结构域相关的机制。
Using fluorescent variants of Fas and FasL, we show that membrane FasL and Fas form supramolecular clusters that are of flexible shape, but nevertheless stable and persistent. Membrane FasL-induced Fas clusters were formed in caspase-8– or FADD-deficient cells or when a cytoplasmic deletion mutant of Fas was used suggesting that cluster formation is independent of the assembly of the cytoplasmic Fas signaling complex and downstream activated signaling pathways. In contrast, cross-linked soluble FasL failed to aggregate the cytoplasmic deletion mutant of Fas, but still induced aggregation of signaling competent full-length Fas. Moreover, membrane FasL-induced Fas cluster formation occurred in the presence of the lipid raft destabilizing component methyl-β-cyclodextrin, whereas Fas aggregation by soluble FasL was blocked. Together, these data suggest that the extracellular domains of Fas and FasL alone are sufficient to drive membrane FasL-induced formation of supramolecular Fas–FasL complexes, whereas soluble FasL-induced Fas aggregation is dependent on lipid rafts and mechanisms associated with the intracellular domain of Fas.