Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Nat Chem Biol. 2019 Aug;15(8):838-845. doi: 10.1038/s41589-019-0321-7. Epub 2019 Jul 18.
Excreted small-molecule signals can bias developmental trajectories and physiology in diverse animal species. However, the chemical identity of these signals remains largely obscure. Here we report identification of an unusual N-acylated glutamine derivative, nacq#1, that accelerates reproductive development and shortens lifespan in Caenorhabditis elegans. Produced predominantly by C. elegans males, nacq#1 hastens onset of sexual maturity in hermaphrodites by promoting exit from the larval dauer diapause and by accelerating late larval development. Even at picomolar concentrations, nacq#1 shortens hermaphrodite lifespan, suggesting a trade-off between reproductive investment and longevity. Acceleration of development by nacq#1 requires chemosensation and is dependent on three homologs of vertebrate steroid hormone receptors. Unlike ascaroside pheromones, which are restricted to nematodes, fatty acylated amino acid derivatives similar to nacq#1 have been reported from humans and invertebrates, suggesting that related compounds may serve signaling functions throughout metazoa.
排泄的小分子信号可以影响不同动物物种的发育轨迹和生理机能。然而，这些信号的化学本质在很大程度上仍然不清楚。在这里，我们报告了一种不寻常的 N-酰化谷氨酰胺衍生物，nacz#1，它可以加速秀丽隐杆线虫的生殖发育并缩短其寿命。nacz#1 主要由雄性线虫产生，它通过促进从幼虫 dauer 滞育中退出并加速晚期幼虫发育来加速雌雄同体的性成熟。即使在皮摩尔浓度下，nacz#1 也会缩短雌雄同体的寿命，这表明生殖投资和寿命之间存在权衡。nacz#1 对发育的加速作用需要化学感觉，并依赖于三种脊椎动物类固醇激素受体的同源物。与局限于线虫的信息素类 ascrosides 不同，类似 nacz#1 的脂肪酸酰化氨基酸衍生物已在人类和无脊椎动物中被报道，这表明相关化合物可能在后生动物中发挥信号功能。
