The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila
The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila
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DOI：
10.1242/dev.01790
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发表时间：
2005-05-01
期刊：
影响因子：
4.6
通讯作者：
Bergmann, A
中科院分区：
文献类型：
--
作者：
Xu, DB;Li, Y;Bergmann, A
启动子caspase Dronc是唯一一个含有caspase激活和募集结构域（CARD）的果蝇caspase。虽然Dronc被认为是细胞凋亡的重要效应子，但由于Dronc突变体尚未发现，因此Dronc在正常发育中的遗传功能尚不清楚。在EMS诱变筛选中，我们分离出dronc中的四个点突变，这些点突变重新抑制由眼睛特异性HID过表达引起的眼睛消融表型。纯合子突变dronc动物死亡蛹阶段，然而，在一个低频率，我们获得了纯合子成年逃生。这些逃生者的眼睛和翅膀中有额外的细胞，这些细胞不太透明且稍微向下弯曲。我们确定这是由于缺乏凋亡。我们对dronc突变胚胎的分析表明，dronc是果蝇发育过程中大多数凋亡细胞死亡所必需的，但它们也意味着存在一个dronc独立的细胞死亡途径。我们还构建了dronc和凋亡抑制剂diap1的双突变果蝇。dronc突变体可以挽救由diap1突变引起的卵巢变性表型，证实dronc在diap1的遗传下游起作用。
The initiator caspase Dronc is the only Drosophild caspase that contains a caspase activation and recruitment domain (CARD). Although Dronc has been implicated as an important effector of apoptosis, the genetic function of dronc in normal development is unclear because dronc mutants have not been available. In an EMS mutagenesis screen, we isolated four point mutations in dronc that recessively suppress the eye ablation phenotype caused by eye-specific overexpression of hid. Homozygous mutant dronc animals die during pupal stages; however, at a low frequency we obtained homozygous adult escapers. These escapers have additional cells in the eye and wings that are less transparent and slightly curved down. We determined that this is due to lack of apoptosis. Our analyses of dronc mutant embryos suggest that dronc is essential for most apoptotic cell death during Drosophila development, but they also imply the existence of a dronc-independent cell death pathway. We also constructed double mutant flies for dronc and the apoptosis inhibitor diap1. dronc mutants can rescue the ovarian degeneration phenotype caused by diap1 mutations, confirming that dronc acts genetically downstream of diap1.