Phagocytosis promotes programmed cell death in C-elegans

Phagocytosis promotes programmed cell death in C-elegans
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DOI:
10.1038/35084096
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发表时间:
2001-07-12
期刊:
影响因子:
64.8
通讯作者:
Horvitz, HR
Horvitz, HR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Reddien, PW;Cameron, S;Horvitz, HR

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在线虫中,细胞程序性死亡需要杀伤基因egl-1、ce-4和ce-3(参考文献1和2),死亡细胞的吞噬需要基因ce-1、ce-2、ce-5、ce-6、ce-7、ce-10和ce-12(参考文献3-5)。在这里,我们展示了吞噬促进细胞程序性死亡。导致杀手基因部分功能丧失的突变允许一些编程死亡的细胞存活,而吞噬基因的突变提高了这种细胞存活的频率。此外,吞噬基因的突变本身就允许一些通常会死亡的细胞存活和分化。吞噬基因可能作用于吞噬细胞以促进死亡,因为Ced-1在吞噬细胞中的表达,编码一种识别细胞身体的受体,拯救了Ced-1突变体的细胞杀伤缺陷。我们认为吞噬细胞的作用是确保由CED-3 caspase(7)触发的细胞发生程序性死亡,而不是在死亡的初始阶段后恢复。
In the nematode Caenorhabditis elegans programmed cell death requires the killer genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dying cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs 3-5). Here we show that engulfment promotes programmed cell death. Mutations that cause partial loss of function of killer genes allow the survival of some cells that are programmed to die, and mutations in engulfment genes enhance the frequency of this cell survival. Furthermore, mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die. Engulfment genes probably act in engulfing cells to promote death, as the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses(6), rescues the cell-killing defects of ced-1 mutants. We propose that engulfing cells act to ensure that cells triggered to undergo programmed cell death by the CED-3 caspase(7) die rather than recover after the initial stages of death.