Department of Biosciences and Nutrition, Center for Biosciences at NOVUM, Karolinska Institute, Huddinge, Sweden.
PLoS One. 2011 Jan 27;6(1):e16561. doi: 10.1371/journal.pone.0016561.
Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.
硫氧还蛋白包含一个保守的氧化还原调节剂家族，参与许多生物学过程，包括应激抵抗和衰老。我们报告说，秀丽隐杆线虫的硫氧还蛋白 TRX-1 在 ASJ 头部感觉神经元中作为一种新型的胰岛素样神经肽 DAF-28 的调节剂，参与 dauer 形成。我们表明，在编码胰岛素样神经肽 DAF-28 的基因发生突变的情况下，增加应激抵抗、长寿命 dauer 幼虫的形成需要 TRX-1 在 ASJ 神经元中发挥作用，位于胰岛素样受体 DAF-2 的上游。遗传挽救实验表明，TRX-1 在 ASJ 神经元中的氧化还原非依赖性功能对于 dauer 形成组成型（Daf-c）表型的 daf-28 突变体是必需的。trx-1 和 daf-28 的 GFP 报告基因在 dauer 中表现出相反的表达模式（即 trx-1 上调，daf-28 下调），而在生长中的 L2/L3 幼虫中则没有观察到这种现象。此外，在 dauer 形成过程中，功能性 TRX-1 对于 daf-28 GFP 报告基因的下调是必需的，这一过程可能受到 DAF-28 介导的反馈调节。我们的研究结果表明，TRX-1 通过参与 dauer 形成过程中 daf-28 表达的下调来调节 DAF-28 信号。我们提出，TRX-1 作为 ASJ 神经元内的一个波动神经元信号调节剂，监测神经肽表达的调整，包括在 dauer 形成过程中对不利环境条件的胰岛素样蛋白的表达。
