当前位置: X-MOL 学术Curr. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Evolutionarily Conserved Regulation of Sleep by the Protein Translational Regulator PERK.
Current Biology ( IF 8.1 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.cub.2020.02.030
Sarah Ly 1 , Daniel A Lee 2 , Ewa Strus 1 , David A Prober 2 , Nirinjini Naidoo 1
Affiliation  

Sleep is a cross-species phenomenon whose evolutionary and biological function remain poorly understood. Clinical and animal studies suggest that sleep disturbance is significantly associated with disruptions in protein homeostasis-or proteostasis-in the brain, but the mechanism of this link has not been explored. In the cell, the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway modulates proteostasis by transiently inhibiting protein synthesis in response to proteostatic stress. In this study, we examined the role of the PERK pathway in sleep regulation and provide the first evidence that PERK signaling is required to regulate normal sleep in both vertebrates and invertebrates. We show that pharmacological inhibition of PERK reduces sleep in both Drosophila and zebrafish, indicating an evolutionarily conserved requirement for PERK in sleep. Genetic knockdown of PERK activity also reduces sleep in Drosophila, whereas PERK overexpression induces sleep. Finally, we demonstrate that changes in PERK signaling directly impact wake-promoting neuropeptide expression, revealing a mechanism through which proteostatic pathways can affect sleep and wake behavior. Taken together, these results demonstrate that protein synthesis pathways like PERK could represent a general mechanism of sleep and wake regulation and provide greater insight into the relationship between sleep and proteostasis.

中文翻译:

蛋白质翻译调节剂 PERK 对睡眠的进化保守调节。

睡眠是一种跨物种现象,其进化和生物学功能仍然知之甚少。临床和动物研究表明,睡眠障碍与大脑中蛋白质稳态或蛋白质稳态的破坏显着相关,但尚未探索这种联系的机制。在细胞中,蛋白激酶 R (PKR) 样内质网激酶 (PERK) 通路通过瞬时抑制蛋白质合成以响应蛋白质稳态应激来调节蛋白质稳态。在这项研究中,我们检查了 PERK 通路在睡眠调节中的作用,并提供了第一个证据表明 PERK 信号传导是调节脊椎动物和无脊椎动物的正常睡眠所必需的。我们表明 PERK 的药理抑制作用会减少果蝇和斑马鱼的睡眠,表明在睡眠中对 PERK 的进化保守要求。PERK 活性的基因敲除也会减少果蝇的睡眠,而 PERK 过表达会诱导睡眠。最后,我们证明了 PERK 信号的变化直接影响促进唤醒的神经肽的表达,揭示了蛋白质抑制通路可以影响睡眠和唤醒行为的机制。总之,这些结果表明,像 PERK 这样的蛋白质合成途径可以代表睡眠和觉醒调节的一般机制,并提供对睡眠和蛋白质稳态之间关系的更深入了解。揭示了一种机制,通过该机制,蛋白质通路可以影响睡眠和清醒行为。总之,这些结果表明,像 PERK 这样的蛋白质合成途径可以代表睡眠和觉醒调节的一般机制,并提供对睡眠和蛋白质稳态之间关系的更深入了解。揭示了一种机制,通过该机制,蛋白质通路可以影响睡眠和清醒行为。总之,这些结果表明,像 PERK 这样的蛋白质合成途径可以代表睡眠和觉醒调节的一般机制,并提供对睡眠和蛋白质稳态之间关系的更深入了解。
更新日期:2020-03-12
down
wechat
bug