Pumilio Regulates Sleep Homeostasis in Response to Chronic Sleep Deprivation in Drosophila melanogaster

Abstract

Recent studies have identified the Drosophila brain circuits involved in the sleep/wake switch and have pointed to the modulation of neuronal excitability as one of the underlying mechanisms triggering sleep need. In this study we aimed to explore the link between the homeostatic regulation of neuronal excitability and sleep behavior in the circadian circuit. For this purpose, we selected Pumilio (Pum), whose main function is to repress protein translation and has been linked to modulation of neuronal excitability during chronic patterns of altered neuronal activity. Here we explore the effects of Pum on sleep homeostasis in Drosophila melanogaster, which shares most of the major features of mammalian sleep homeostasis. Our evidence indicates that Pum is necessary for sleep rebound and that its effect is more pronounced during chronic sleep deprivation (84 h) than acute deprivation (12 h). Knockdown of pum, results in a reduction of sleep rebound during acute sleep deprivation and the complete abolishment of sleep rebound during chronic sleep deprivation. Based on these findings, we propose that Pum is a critical regulator of sleep homeostasis through neural adaptations triggered during sleep deprivation.

Homeostatic control of deep sleep and molecular correlates of sleep pressure in Drosophila

“…The vinegar fly Drosophila melanogaster has proved to be a useful model organism for understanding the molecular and cellular mechanisms regulating sleep ( Hendricks et al, 2000 ; Shaw et al, 2000 ). The powerful genetic tools available in flies, along with the ability to manipulate and measure neural signaling within small groups of defined cell types, have revealed genes and brain networks that mediate the homeostatic regulation of sleep ( DeJesúsOlmo et al, 2020 ; Donlea et al, 2014 ; Ni et al, 2019 ; Seidner et al, 2015 ). Furthermore, such work in the fly has revealed mechanisms that also regulate sleep in mammals ( Liu et al, 2016 ; Shafer and Keene, 2021 ).…”

Integrated Screening of Effective Anti-Insomnia Fractions of Zhi-Zi-Hou-Po Decoction via Drosophila melanogaster and Network Pharmacology Analysis of the Underlying Pharmacodynamic Material and Mechanism

“…Luis published the regulation of homeostasis in neuronal excitability through sleep behavior, in which they researched the effects of Pumilio (Pum) on sleep homeostasis in D. melanogaster , and had identified Pum action on neural adaptations. 10 Wang utilized Drosophila for screening of sleep-assisting drugs and ranked the drug potency based on different aspects of sleep regulation. 11 In the initial stage, our group successfully constructed the Drosophila model of sleep deprivation and preceded the pharmacodynamics study of Shuangxia decoction in the treatment of insomnia.…”

Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay

“…Drosophila Pumilio-the founding member of the PUM family -is characterized as a translational repressor and is involved in embryo patterning, fertility and the regulation of neuronal homeostasis 31,[37][38][39][40] . PUM proteins act as post-transcriptional regulators, by interacting with consensus sequences called Pumilio regulatory elements (PRE) in the 3′UTRs of target mRNAs 9 to modulate their translation and/or degradation 41,42 .…”