Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis.

中文翻译：

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胰岛素/IGF-1 信号诱导的膳食肽摄取通过 PEPT-1 对种系蛋白质稳态的非细胞自主调节。


配子发生涉及活性蛋白质合成，并被认为依赖于蛋白质稳态。我们之前在秀丽隐杆线虫中的研究表明，种系发育需要胰岛素/IGF-1 信号传导 （IIS） 和 HSF-1（热休克反应的中心调节因子）的协调活动。然而，下游机制尚未确定。在这里，我们表明生殖细胞中 HSF-1 的消耗会损害伴侣基因表达，导致蛋白质降解和聚集，从而降低繁殖力和配子质量。相反，IIS 降低赋予生殖细胞对 HSF-1 耗竭诱导的蛋白质折叠缺陷和各种蛋白毒性应激的恢复力。令人惊讶的是，这种效应不是由增强的应激反应介导的，这是在低 IIS 条件下长寿的基础，而是通过降低核糖体生物发生和翻译速率介导的。我们发现 IIS 通过减轻 FOXO/DAF-16 对肠道肽转运蛋白 PEPT-1 的抑制来激活肠道肽转运蛋白 PEPT-1 的表达，使膳食蛋白质能够有效地掺入为种系蛋白质合成提供燃料的氨基酸库中。我们的数据表明，这种非细胞自主途径对于配子发生过程中的蛋白质稳态调节至关重要。