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Embryo integrity regulates maternal proteostasis and stress resilience.
Genes & Development ( IF 10.5 ) Pub Date : 2020-03-26 , DOI: 10.1101/gad.335422.119
Ambre J Sala 1 , Laura C Bott 1 , Renee M Brielmann 1 , Richard I Morimoto 1
Affiliation  

The proteostasis network is regulated by transcellular communication to promote health and fitness in metazoans. In Caenorhabditis elegans, signals from the germline initiate the decline of proteostasis and repression of cell stress responses at reproductive maturity, indicating that commitment to reproduction is detrimental to somatic health. Here we show that proteostasis and stress resilience are also regulated by embryo-to-mother communication in reproductive adults. To identify genes that act directly in the reproductive system to regulate somatic proteostasis, we performed a tissue targeted genetic screen for germline modifiers of polyglutamine aggregation in muscle cells. We found that inhibiting the formation of the extracellular vitelline layer of the fertilized embryo inside the uterus suppresses aggregation, improves stress resilience in an HSF-1-dependent manner, and restores the heat-shock response in the somatic tissues of the parent. This pathway relies on DAF-16/FOXO activation in vulval tissues to maintain stress resilience in the mother, suggesting that the integrity of the embryo is monitored by the vulva to detect damage and initiate an organismal protective response. Our findings reveal a previously undescribed transcellular pathway that links the integrity of the developing progeny to proteostasis regulation in the parent.

中文翻译:

胚胎的完整性调节着母体的蛋白质变形和压力弹性。

蛋白质稳定网络由跨细胞通讯调节,以促进后生动物的健康和适应。在秀丽隐杆线虫中,来自生殖系的信号在繁殖成熟时启动了蛋白稳态下降和细胞应激反应的抑制,表明对生殖的承诺不利于身体健康。在这里,我们表明,在成年成年人中,蛋白质稳态和应激弹性也受到胚胎与母亲之间的沟通的调节。为了鉴定直接在生殖系统中起作用以调节体细胞蛋白稳态的基因,我们对肌肉细胞中聚谷氨酰胺聚集的种系修饰剂进行了针对组织的遗传筛选。我们发现抑制子宫内受精胚胎的细胞外卵黄质层的形成可以抑制聚集,以HSF-1依赖的方式改善应激弹性,并恢复亲本体细胞组织的热激反应。该途径依赖于外阴组织中的DAF-16 / FOXO活化以维持母亲的应激弹性,这表明外阴可监测胚胎的完整性以检测损伤并启动机体保护反应。我们的发现揭示了以前未描述的跨细胞途径,该途径将发育中子代的完整性与亲本中的蛋白稳态调节联系在一起。这表明外阴可监控胚胎的完整性,以检测损伤并引发机体保护性反应。我们的发现揭示了以前未描述的跨细胞途径,该途径将发育中子代的完整性与亲本中的蛋白稳态调节联系在一起。这表明外阴可监测胚胎的完整性,以检测损伤并引发机体保护性反应。我们的发现揭示了以前未描述的跨细胞途径,该途径将发育中子代的完整性与亲本中的蛋白稳态调节联系在一起。
更新日期:2020-05-01
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