Ascaroside signaling in C. elegans.
Ascaroside signaling in C. elegans.
复制标题
DOI：
10.1895/wormbook.1.155.1
复制
发表时间：
2013-01-18
期刊：
影响因子：
--
通讯作者：
Schroeder FC
中科院分区：
文献类型：
--
作者：
Ludewig AH;Schroeder FC
在过去的10年里，小分子信号在秀丽隐杆线虫发育和行为的许多方面的相关性已经变得明显。一组突出的小分子信号是蛔虫苷，它控制着水的进出以及各种性别特异性和社会行为，包括雄性吸引、雌雄同体排斥、嗅觉可塑性和聚集。天车甙化学结构的多样性促进了其广泛的生物学功能。这些都是基于糖蛔虫糖，它与不同长度的脂肪酸样侧链相连，并且通常用氨基酸、叶酸和其他初级代谢物衍生的构建块进一步修饰。不同的蛔虫苷或蛔虫苷的组合介导不同的表型，甚至化学结构的微小差异往往与强烈改变的活性谱有关。额外的复杂性来自于浓度依赖效应和不同蛔虫苷之间的协同作用。蛔虫苷可被几种化学感觉头神经元感知，包括ASK、ASI和ADL神经元以及男性特异性CEM神经元。天冬苷感知是由多种g蛋白偶联膜受体家族介导的，这些受体家族作用于保守信号转导途径的上游，包括胰岛素/IGF-1信号通路和转化生长因子β (TGF-β)信号通路。蛔虫苷的生物合成似乎整合了几个主要代谢途径的输入，包括长链脂肪酸的过氧化物酶体氧化和氨基酸分解代谢。生命阶段、性别、食物供应和其他环境因素都会影响阿斯卡罗苷的生物合成，这表明阿斯卡罗罗苷信号传递了生活史和代谢状态的详细信息。
Over the past 10 years, the relevance of small-molecule signaling for many aspects of C. elegans development and behavior has become apparent. One prominent group of small-molecule signals are the ascarosides, which control dauer entry and exit as well as a variety of sex-specific and social behaviors, including male attraction, hermaphrodite repulsion, olfactory plasticity, and aggregation. This wide range of biological functions is facilitated by a great diversity of ascaroside chemical structures. These are based on the sugar ascarylose, which is linked to fatty acid-like side chains of varying lengths and often decorated further with building blocks derived from amino acids, folate, and other primary metabolites. Different ascarosides or combinations of ascarosides mediate different phenotypes, and even small differences in chemical structures are often associated with strongly altered activity profiles. Additional complexity arises from concentration-dependent effects and synergism between different ascarosides. The ascarosides are sensed by several types of chemosensory head neurons, including the ASK, ASI, and ADL neurons as well as the male-specific CEM neurons. Ascaroside perception is mediated by diverse families of G-protein coupled membrane receptors that act upstream of conserved signal transduction pathways, including insulin/IGF-1 signaling and transforming growth factor beta (TGF-β) signaling. Biosynthesis of the ascarosides appears to integrate input from several primary metabolic pathways, including peroxisomal β-oxidation of long-chain fatty acids and amino acid catabolism. Life stage, sex, as well as food availability and other environmental factors affect ascaroside biosynthesis, suggesting that ascaroside signaling communicates detailed information about life history and metabolic state.