C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling.
C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling.
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DOI：
10.1016/j.cub.2008.06.060
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发表时间：
2008-08-05
期刊：
影响因子：
9.2
通讯作者：
Meyer, Barbara J.
中科院分区：
文献类型：
--
作者：
Reiner, David J.;Ailion, Michael;Thomas, James H.;Meyer, Barbara J.
不同的环境刺激，包括暴露于dauer信息素，食物剥夺和高温，可以诱导C。elegans幼虫进入dauer阶段，发育停滞滞育状态。虽然分子和细胞途径负责检测dauer信息素和温度已被部分定义，其他感官输入知之甚少，这些不同的感官输入整合，以实现一致的发展结果的机制。在本文中，我们分析了一个野生C。从沙漠绿洲中分离出来的一种线虫。与野生型实验室菌株不同，沙漠菌株在25°C时对dauer信息素没有反应，但在更高的温度下会有反应，这表明它对炎热的沙漠环境有独特的适应性。我们在dauer反应中将这种缺陷映射到scd-2基因的突变，我们发现scd-2基因编码线虫间变性淋巴瘤激酶（ALK）同源物，一种原癌基因受体酪氨酸激酶。scd-2在此处显示的遗传途径中起作用，包括HEN-1配体、RTK衔接子SOC-1和MAP激酶SMA-5。SCD-2通路调节TGF-β信号传导，其介导对dauer信息素的反应，但SCD-2可能介导非信息素感觉输入，例如食物。我们的研究确定了一种新的控制dauer形成的感觉通路，并阐明了ALK信号传导，信号传导通路的整合以及对极端环境条件的适应。
Different environmental stimuli, including exposure to dauer pheromone, food deprivation, and high temperature, can induce C. elegans larvae to enter the dauer stage, a developmentally arrested diapause state. Although molecular and cellular pathways responsible for detecting dauer pheromone and temperature have been defined in part, other sensory inputs are poorly understood, as are the mechanisms by which these diverse sensory inputs are integrated to achieve a consistent developmental outcome. In this paper, we analyze a wild C. elegans strain isolated from a desert oasis. Unlike wild-type laboratory strains, the desert strain fails to respond to dauer pheromone at 25°C, but it does respond at higher temperatures, suggesting a unique adaptation to the hot desert environment. We map this defect in dauer response to a mutation in the scd-2 gene, which, we show, encodes the nematode anaplastic lymphoma kinase (ALK) homolog, a proto-oncogene receptor tyrosine kinase. scd-2 acts in a genetic pathway shown here to include the HEN-1 ligand, the RTK adaptor SOC-1, and the MAP kinase SMA-5. The SCD-2 pathway modulates TGF-β signaling, which mediates the response to dauer pheromone, but SCD-2 might mediate a nonpheromone sensory input, such as food. Our studies identify a new sensory pathway controlling dauer formation and shed light on ALK signaling, integration of signaling pathways, and adaptation to extreme environmental conditions.
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