Stage-specific regulation of caspase activity in Drosophila oogenesis

Stage-specific regulation of caspase activity in Drosophila oogenesis
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DOI:
10.1016/s0012-1606(03)00240-9
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发表时间:
2003-08-01
影响因子:
2.7
通讯作者:
McCall, K
McCall, K
中科院分区:
生物学3区
文献类型:
--
作者:
Peterson, JS;Barkett, M;McCall, K

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在果蝇卵子发生中,生殖细胞的程序性死亡主要发生在三个不同的阶段。这些细胞死亡受到不同的调控,因为早期和中期的细胞死亡是由胁迫诱导的,而后期卵子发生中的哺育细胞的细胞死亡是发育调节的。在这份报告中,我们表明,在卵子发生的中期和晚期,效应器caspase Drice在细胞死亡期间都被激活,但活性的水平和定位因阶段而异。Active Drice在卵子发生后期的哺育细胞死亡过程中形成局部聚集体,而在中期发生的生殖细胞死亡过程中发现更普遍且水平更高的活性Drice。由于Drice的活性在卵子发生后期是有限的,我们研究了另一种效应caspase,DCP-1,是否可以驱动在卵子发生后期正常发生的独特的形态事件。我们发现,Caspase效应器DCP-1的过早激活导致了丝状肌动蛋白的消失,而不是肌动蛋白束的形成,这表明DCP-1的活性在卵子发生的后期也必须受到抑制。Caspase抑制剂DIAP1的过表达抑制了DCP-1诱导的细胞死亡,但对卵子发生后期的细胞死亡没有影响。这种濒临死亡的哺乳细胞中有限的caspase激活可能会防止哺育细胞的细胞骨架和相连的卵母细胞遭到破坏。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
In Drosophila oogenesis, the programmed cell death of germline cells occurs predominantly at three distinct stages. These cell deaths are subject to distinct regulatory controls, as cell death during early and midoogenesis is stress-induced, whereas the cell death of nurse cells in late oogenesis is developmentally regulated. In this report, we show that the effector caspase Drice is activated during cell death in both mid- and late oogenesis, but that the level and localization of activity differ depending on the stage. Active Drice formed localized aggregates during nurse cell death in late oogenesis; however, active Drice was found more ubiquitously and at a higher level during germline cell death in midoogenesis. Because Drice activity was limited in late oogenesis, we examined whether another effector caspase, Dcp-1, could drive the unique morphological events that occur normally in late oogenesis. We found that premature activation of the effector caspase, Dcp-1, resulted in a disappearance of filamentous actin, rather than the formation of actin bundles, suggesting that Dcp-1 activity must also be restrained in late oogenesis. Overexpression of the caspase inhibitor DIAP1 suppressed cell death induced by Dcp-1 but had no effect on cell death during late oogenesis. This limited caspase activation in dying nurse cells may prevent destruction of the nurse cell cytoskeleton and the connected oocyte. (C) 2003 Elsevier Science (USA). All rights reserved.