C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival
C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival
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DOI：
10.1101/gad.384506
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发表时间：
2006-08-15
影响因子：
10.5
通讯作者：
Hengartner, Michael O.
中科院分区：
文献类型：
--
作者：
Kritikou, Ekaterini A.;Milstein, Stuart;Hengartner, Michael O.
在秀丽隐杆线虫卵母细胞发育过程中，大约一半的发育中的生殖细胞发生凋亡。虽然这一过程从蠕虫到人类在进化上是保守的，但生殖细胞死亡的调节因子在很大程度上仍是未知的。在一个新的基因参与生殖细胞凋亡秀丽隐杆线虫的遗传筛选，我们确定和克隆gla-3。gla-3功能的丧失导致生殖细胞凋亡增加和幼仔数量减少，这是由于减数分裂I中粗线期退出缺陷所致。gla-3编码TIS 11样含锌指蛋白，其在生殖系中表达，从L4幼虫期到成年期。生化证据和遗传上位性分析表明，GLA-3参与MAPK信号级联，并直接与C.秀丽隐杆线虫MAPK MPK-1，一种重要的减数分裂调节因子。我们的研究结果表明，GLA-3是MAPK级联的一个新的组成部分，控制减数分裂进程和细胞凋亡在C。在线虫生殖系中，它在外阴发育和肌肉细胞中作为MAPK信号通路的负调节剂发挥作用。
During oocyte development in Caenorhabditis elegans, approximately half of all developing germ cells undergo apoptosis. While this process is evolutionarily conserved from worms to humans, the regulators of germ cell death are still largely unknown. In a genetic screen for novel genes involved in germline apoptosis in Caenorhabditis elegans, we identified and cloned gla-3. Loss of gla-3 function results in increased germline apoptosis and reduced brood size due to defective pachytene exit from meiosis I. gla-3 encodes a TIS11-like zinc-finger-containing protein that is expressed in the germline, from the L4 larval stage to adulthood. Biochemical evidence and genetic epistasis analysis revealed that GLA-3 participates in the MAPK signaling cascade and directly interacts with the C. elegans MAPK MPK-1, an essential meiotic regulator. Our results show that GLA-3 is a new component of the MAPK cascade that controls meiotic progression and apoptosis in the C. elegans germline and functions as a negative regulator of the MAPK signaling pathway during vulval development and in muscle cells.