核因子结合κ轻链在B细胞(NFκB)涉及广泛的细胞过程,包括发育,增长,先天免疫,和睡眠。然而,在了解特定NFκB转录因子在睡眠中的作用方面的努力有限。果蝇携带三个编码NFκB转录因子的基因,背侧,背部免疫因子(Dif),和美味。我们以前发现,脂肪体内的Relish基因丢失会抑制每天的夜间睡眠,并废除了感染引起的睡眠。在这里,我们表明,Dif调节日常睡眠和长时间清醒后的恢复睡眠。Dif的突变体显示出每日睡眠减少,并抑制了对睡眠剥夺的恢复。Dif的泛神经元敲除强烈抑制了日常睡眠,表明与Relish相比,Dif从中枢神经系统起调节睡眠的作用。根据Dif关联的GAL4驱动程序的分布,我们假设其对睡眠的影响是由大脑间壁(PI)介导的。尽管PI中Dif的RNAi敲除减少了日常睡眠,它对睡眠剥夺的恢复反应没有影响。然而,当Dif的RNAi敲除分布在更广泛的神经元上时,恢复睡眠被抑制。在Dif突变体中,通过睡眠剥夺对nemuri(nur)抗菌肽的诱导受到抑制,nur的泛神经元过表达也抑制了Dif突变体表型。一起,这些发现表明,Dif的功能从大脑到目标nemuri和促进睡眠。
■NFκB转录因子驱动炎症过程,这是伴随睡眠障碍的多种人类疾病的基础。然而,在哺乳动物中研究NFκB在睡眠中的功能的遗传研究受到限制。在果蝇中使用遗传方法,我们证明了DifNFκB,与人类NFκBs的Rel家族同源,从神经元组织起调节日常睡眠和调节对睡眠不足的反应。这些发现增强了我们对特定NFκB基因在睡眠调节中的作用的理解。
The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, efforts have been limited toward understanding how specific NFκB transcription factors function in sleep. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (
Dif), and Relish. We previously found that loss of the Relish gene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show that
Dif regulates daily sleep and recovery sleep following prolonged wakefulness. Mutants of
Dif showed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown of Dif strongly suppressed daily sleep, indicating that in contrast to Relish,
Dif functions from the central nervous system to regulate sleep. Based on the distribution of a Dif-associated GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down of Dif in the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down of Dif was distributed across a wider range of neurons. Induction of the nemuri (nur) antimicrobial peptide by sleep deprivation was suppressed in Dif mutants and pan-neuronal over-expression of nur also suppressed the
Dif mutant phenotype. Together, these findings indicate that Dif functions from brain to target nemuri and to promote sleep.