NPP-16/Nup50 function and CDK-1 inactivation are associated with anoxia-induced prophase arrest in Caenorhabditis elegans.

NPP-16/Nup50 function and CDK-1 inactivation are associated with anoxia-induced prophase arrest in Caenorhabditis elegans.
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DOI:
10.1091/mbc.e09-09-0787
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发表时间:
2010-03-01
影响因子:
3.3
通讯作者:
Padilla PA
Padilla PA
中科院分区:
生物学3区
文献类型:
--
作者:
Hajeri VA;Little BA;Ladage ML;Padilla PA

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细胞和遗传分析支持NPP-16/NUP50和CDK-1功能可逆性地阻止秀丽线虫胚胎在缺氧条件下的早期分裂球的概念。缺氧诱导的细胞从活跃分裂状态到停滞状态的转变揭示了线虫胚胎中一个以前未描述的前期检查点。氧是一种基本的营养物质,通过多种细胞途径感受到,这些途径促进了对缺氧的反应和生存。秀丽线虫胚胎暴露在严重的缺氧(缺氧)中,进入了一种暂停的状态,在这种状态下,细胞周期进程在特定的阶段可逆地停止。对缺氧反应的间期、前期或中期停滞的调节机制尚不完全清楚。受阻的早期分裂球和卵母细胞的特征是核周浓缩的染色体排列和核膜破裂受阻。值得注意的是,在缺乏NPP-16/NUP50功能的突变胚胎中,缺氧诱导的早期停滞被抑制,这表明该核孔蛋白在野生型胚胎的早期停滞中发挥了重要作用。虽然在野生型受阻的早期卵裂球中检测到了细胞周期蛋白依赖性激酶(CDK-1)的失活形式,但在缺氧暴露的NPP-16突变体中没有检测到失活状态。此外,我们还发现CDK-1定位于缺氧胚胎的染色体附近。这些数据支持NPP-16和CDK-1在线虫胚胎中阻止早期裂球的功能。缺氧诱导的细胞从活跃分裂状态到停滞状态的转变揭示了线虫胚胎中一个以前未描述的前期检查点。
Cellular and genetic analysis supports the notion that NPP-16/NUP50 and CDK-1 function to reversibly arrest prophase blastomeres in Caenorhabditis elegans embryos exposed to anoxia. The anoxia-induced shift of cells from an actively dividing state to an arrested state reveals a previously uncharacterized prophase checkpoint in the C. elegans embryo. Oxygen, an essential nutrient, is sensed by a multiple of cellular pathways that facilitate the responses to and survival of oxygen deprivation. The Caenorhabditis elegans embryo exposed to severe oxygen deprivation (anoxia) enters a state of suspended animation in which cell cycle progression reversibly arrests at specific stages. The mechanisms regulating interphase, prophase, or metaphase arrest in response to anoxia are not completely understood. Characteristics of arrested prophase blastomeres and oocytes are the alignment of condensed chromosomes at the nuclear periphery and an arrest of nuclear envelope breakdown. Notably, anoxia-induced prophase arrest is suppressed in mutant embryos lacking nucleoporin NPP-16/NUP50 function, indicating that this nucleoporin plays an important role in prophase arrest in wild-type embryos. Although the inactive form of cyclin-dependent kinase (CDK-1) is detected in wild-type–arrested prophase blastomeres, the inactive state is not detected in the anoxia exposed npp-16 mutant. Furthermore, we found that CDK-1 localizes near chromosomes in anoxia-exposed embryos. These data support the notion that NPP-16 and CDK-1 function to arrest prophase blastomeres in C. elegans embryos. The anoxia-induced shift of cells from an actively dividing state to an arrested state reveals a previously uncharacterized prophase checkpoint in the C. elegans embryo.
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