PDF(Pubmed)
Abstract：
Insulin/IGF signaling (IIS) regulates developmental and metabolic plasticity. Conditional regulation of insulin-like peptide expression and secretion promotes different phenotypes in different environments. However, IIS can also be regulated by other, less-understood mechanisms. For example, stability of the only known insulin/IGF receptor in C. elegans, DAF-2/INSR, is regulated by CHIP-dependent ubiquitination. Disruption of chn-1/CHIP reduces longevity in C. elegans by increasing DAF-2/INSR abundance and IIS activity in adults. Likewise, mutation of a ubiquitination site causes daf-2(gk390525) to display gain-of-function phenotypes in adults. However, we show that this allele displays loss-of-function phenotypes in larvae, and that its effect on IIS activity transitions from negative to positive during development. In contrast, the allele acts like a gain-of-function in larvae cultured at high temperature, inhibiting temperature-dependent dauer formation. Disruption of chn-1/CHIP causes an increase in IIS activity in starved L1 larvae, unlike daf-2(gk390525). CHN-1/CHIP ubiquitinates DAF-2/INSR at multiple sites. These results suggest that the sites that are functionally relevant to negative regulation of IIS vary in larvae and adults, at different temperatures, and in nutrient-dependent fashion, revealing additional layers of IIS regulation.
摘要：
胰岛素/IGF信号(IIS)调节发育和代谢可塑性。胰岛素样肽表达和分泌的条件调节在不同环境中促进不同表型。然而,IIS也可以由其他了解较少的机制。例如,秀丽隐杆线虫中唯一已知的胰岛素/IGF受体的稳定性，DAF-2/INSR,受CHIP依赖性泛素化调节。chn-1/CHIP的破坏通过增加成人的DAF-2/INSR丰度和IIS活性来降低秀丽隐杆线虫的寿命。同样，泛素化位点的突变导致daf-2(gk390525)在成人中显示功能获得表型。然而,我们表明该等位基因在幼虫中表现出功能丧失的表型，在开发过程中，它对IIS活动的影响从负面转变为正面。相比之下,等位基因在高温下培养的幼虫中起着功能增益的作用，抑制温度依赖性道尔形成。chn-1/CHIP的破坏导致饥饿的L1幼虫的IIS活性增加，不同于DAF-2（gk390525）。CHN-1/CHIP在多个位点泛素化DAF-2/INSR。这些结果表明，与IIS负调控功能相关的位点在幼虫和成虫中有所不同，在不同的温度下，以营养依赖的方式，揭示IIS调节的附加层。
■类胰岛素信号在帮助动物适应不同的环境条件中起着至关重要的作用。胰岛素分子丰度的差异驱动胰岛素信号的差异，影响生长，新陈代谢，和对压力条件的抵抗力。在线虫线虫中的先前工作表明，胰岛素受体的靶向降解也调节胰岛素信号传导。我们在这里表明，这个过程受发育阶段的影响，营养可用性，和温度，揭示了胰岛素样信号在这个有价值的动物模型中被调节的其他方式。
■类胰岛素信号在帮助动物适应不同的环境条件中起着至关重要的作用。胰岛素分子丰度的差异驱动胰岛素信号的差异，影响生长，新陈代谢，和对压力条件的抵抗力。在线虫线虫中的先前工作表明，胰岛素受体的靶向降解也调节胰岛素信号传导。我们在这里表明，这个过程受发育阶段的影响，营养可用性，和温度，揭示了胰岛素样信号在这个有价值的动物模型中被调节的其他方式。
