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Dietary restriction and gonadal signaling differentially regulate post‐development quality control functions in Caenorhabditis elegans

机译:饮食限制和性腺信号差异调节秀丽隐杆线虫的发育后质量控制功能

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摘要

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting in a sharp decline in folding capacity and reduced ability to cope with chronic and acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse and reshape the quality control network. Given that environmental conditions, such as food availability, impact reproductive success, we asked whether conditions of dietary restriction (DR) can also reverse the decline in quality control function at the transition to adulthood, and if so, whether gonadal signaling and dietary signaling remodel the quality control network in a similar or different manner. For this, we employed the eat‐2 genetic model and bacterial deprivation protocol. We found that animals under DR maintained heat shock response activation and high protein folding capacity during adulthood. However, while gonadal signaling required DAF‐16, DR‐associated rescue of quality control functions required the antagonistic transcription factor, PQM‐1. Bioinformatic analyses supported a role for DAF‐16 in acute stress responses and a role for PQM‐1 in cellular maintenance and chronic stress. Comparing the stress activation and folding capacities of dietary‐ and gonadal‐signaling mutant animals confirmed this prediction and demonstrated that each differentially impacts cellular quality control capabilities. These data suggest that the functional mode of cellular quality control networks can be differentially remodeled, affecting an organism's ability to respond to acute and chronic stresses during adulthood.
机译:在秀丽隐杆线虫成年期早期,蛋白质稳态得以重塑,导致折叠能力急剧下降,应对慢性和急性应激的能力下降。来自生殖系统的内分泌信号可以改善这种蛋白稳态的崩溃并重塑质量控制网络。考虑到环境条件,例如食物供应,影响生殖成功,我们询问饮食限制条件是否也可以逆转成年后质量控制功能的下降;如果是,性腺信号和饮食信号是否重塑质量控制网络以类似或不同的方式。为此,我们采用了eat-2遗传模型和细菌剥夺方案。我们发现在成年期DR下的动物保持热休克反应激活和高蛋白折叠能力。但是,虽然性腺信号需要DAF-16,但与DR相关的质量控制功能的挽救需要拮抗转录因子PQM-1。生物信息学分析支持DAF-16在急性应激反应中的作用以及PQM-1在细胞维持和慢性应激中的作用。比较饮食信号和性腺信号突变动物的应激激活和折叠能力,证实了这一预测,并证明了每种差异影响细胞质量控制能力。这些数据表明,细胞质量控制网络的功能模式可以进行不同的重塑,从而影响生物体在成年期对急性和慢性应激作出反应的能力。

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