Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone
Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone
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DOI：
10.1038/nature03201
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发表时间：
2005-02-03
期刊：
影响因子：
64.8
通讯作者：
Paik, YK
中科院分区：
文献类型：
--
作者：
Jeong, PY;Jung, M;Paik, YK
信息素是用于同一物种个体之间交流的细胞类型特异性信号。当面临过度拥挤或饥饿时，秀丽隐杆线虫会分泌信息素 daumone，促进个体之间的沟通，以适应不利的环境刺激(1-4)。 Daumone 标志着线虫进入 dauer 阶段，这是线虫生命周期中持久且非衰老的阶段，具有独特的适应性特征和延长的寿命。由于道莫酮是发育和衰老过程中化学感应过程的关键调节剂 (5,6)，因此道莫酮的化学鉴定对于阐明道莫酮介导的信号转导通路的特征非常重要。在这里，我们报告了通过大规模纯化从秀丽隐杆线虫中分离天然道莫酮，以及道莫酮的全化学合成。我们展示了纯化的道莫酮（一种脂肪酸衍生物）的立体特异性化学结构。我们证明，天然和化学合成的道尔酮同样诱导秀丽隐杆线虫（N2菌株）和某些道尔突变体中道尔幼虫的形成，并且还导致食物和道尔酮之间的竞争。这些结果应有助于阐明道酮介导的信号通路，进而可能影响衰老和肥胖研究以及抗线虫药物的开发。
Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli(1-4). Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing(5,6), the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.