RAIDD aggregation facilitates apoptotic death of PC12 cells and sympathetic neurons
RAIDD aggregation facilitates apoptotic death of PC12 cells and sympathetic neurons
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DOI：
10.1038/sj.cdd.4401397
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发表时间：
2004-06-01
影响因子：
12.4
通讯作者：
Stefanis, L
中科院分区：
文献类型：
--
作者：
Jabado, O;Wang, Q;Stefanis, L
在人类细胞系中，半胱天冬酶2衔接子RAIDD通过其半胱天冬酶募集结构域（CARD）选择性地与半胱天冬酶2相互作用，并导致半胱天冬酶2依赖性死亡。RAIDD是否在神经元细胞中诱导这种效应尚不清楚。我们以前已经表明，caspase 2是必不可少的营养因子剥夺的PC12细胞和大鼠交感神经元的凋亡。我们在这里报告，大鼠RAIDD，从PC 12细胞克隆，与大鼠caspase 2 CARD相互作用。RAIDD过表达诱导caspase 2 CARD和caspase 9依赖的PC12细胞和交感神经元凋亡。细胞凋亡与离散核周聚集体的形成相关。死亡和聚集都需要全长RAIDD的表达。这样的聚集体可以通过紧密接近而使胱天蛋白酶2更有效地活化。营养剥夺后，RAIDD过度表达增加死亡和聚集体形成。因此，RAIDD聚集对于其促死作用是重要的，并且可能在营养因子撤药诱导的神经元凋亡中起作用。
In human cell lines, the caspase 2 adaptor RAIDD interacts selectively with caspase 2 through its caspase recruitment domain (CARD) and leads to caspase 2-dependent death. Whether RAIDD induces such effects in neuronal cells is unknown. We have previously shown that caspase 2 is essential for apoptosis of trophic factor-deprived PC12 cells and rat sympathetic neurons. We report here that rat RAIDD, cloned from PC12 cells, interacts with rat caspase 2 CARD. RAIDD overexpression induced caspase 2 CARD- and caspase 9-dependent apoptosis of PC12 cells and sympathetic neurons. Apoptosis correlated with the formation of discrete perinuclear aggregates. Both death and aggregates required the expression of full-length RAIDD. Such aggregates may enable more effective activation of caspase 2 through close proximity. Following trophic deprivation, RAIDD overexpression increased death and aggregate formation. Therefore, RAIDD aggregation is important for its death-promoting effects and may play a role in trophic factor withdrawal-induced neuronal apoptosis.