Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

Konietzka, Jan; Fritz, Maximilian; Spiri, Silvan; McWhirter, Rebecca; Leha, Andreas; Palumbos, Sierra; Costa, Wagner Steuer; Oranth, Alexandra; Gottschalk, Alexander; Miller, David M.; Hajnal, Alex; Bringmann, Henrik

doi:10.1016/j.cub.2019.10.048

Cited by 65 publications

(155 citation statements)

References 91 publications

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“…Mechanistic details of RIS activation are beginning to emerge. RIS, like ALA (see below), responds to the epidermal growth factor EGF (Konietzka et al 2020), but is also activated by excitatory input from several other neurons (Maluck et al 2020). These include the forward command interneuron PVC, suggesting a mechanism by which locomotion circuit activity during wake behavior can influence sleep (Maluck et al 2020).…”

Section: Behavioral Quiescence During Developmentally Timed Sleepmentioning

confidence: 99%

Behavioral States

2020

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Section: Behavioral Quiescence During Developmentally Timed Sleepmentioning

confidence: 99%

Behavioral States

2020

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“…Other possible Pum functions that could have played a role in our results include EGFR and the regulation of inflammatory pathways. EGFR is a direct target of Pum in Drosophila and has been implicated in sleep regulation in flies, worms, zebrafish and humans (Foltenyi et al, 2007;Kim et al, 2012;Lee et al, 2019;Konietzka et al, 2020). These studies showed that EGFR signaling promotes sleep in all organisms tested but its role in sleep homeostasis was only examined in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Innate immunity-induced sleep requires the immune response (STA-2) and AMPs and is thus mechanistically distinct from EGF-induced sleep [15,16,54]. The partial suppression of wounding-induced sleep by immune response genes suggests that perhaps AMP and EGF signaling act in parallel to increase sleep following injury by converging on RIS neuron depolarization [55].…”

Section: Wounding Signals Through Nlps and Cncs To The Nervous Systemmentioning

confidence: 99%

“…Single-cell sequencing showed that NPR-12 is expressed also in RIM neurons [59], which are also involved in RIS activation [58]. However, NPR-12 is not expressed in RIS itself [55]. Thus, NLP-29 signals need for sleep to the nervous system through the NPR-12 neuropeptide receptor that is expressed in the brain.…”

Section: Nlp-29 Acts Through the Neuropeptide Receptor Npr-12mentioning

confidence: 99%

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Antimicrobial peptides signal need for sleep from peripheral wounds to the nervous system

Sinner

Masurat

Ewbank

et al. 2020

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AbstractWounding triggers a protective innate immune response that includes the production of antimicrobial peptides and increased sleep. Little is known, however, about how peripheral wounds signal need for sleep to the nervous system. We found that during C. elegans larval molting, a tolloid/BMP-1-like protein promotes sleep through an epidermal innate immune pathway and the expression of more than a dozen antimicrobial peptide (AMP) genes. In the adult, epidermal injury activates innate immunity and turns up AMP production to trigger sleep. We show for one AMP, NLP-29, that it acts through the neuropeptide receptor NPR-12 in neurons that depolarize the sleep-active RIS neuron to induce sleep. Sleep in turn increases the chance of surviving injury. Thus, we found a novel mechanism by which peripheral wounds signal to the nervous system to increase protective sleep. Such a long-range somnogen signaling function of AMPs might also boost sleep in other animals including humans.Highlights- Gain-of-function mutation in the tolloid/BMP-1-like NAS-38 protein increases sleep- NAS-38 activates innate immunity pathways to ramp up STAT-dependent antimicrobial peptide (AMP) expression- Wounding increases sleep through the innate immune response and AMPs- Antimicrobial peptides are long-range somnogens that act through neuronal neuropeptide receptors to depolarize a sleep-active neuron- Sleep increases the chance to survive injuryGraphical Abstract

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Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

Cited by 65 publications

References 91 publications

Behavioral States

Behavioral States

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

Antimicrobial peptides signal need for sleep from peripheral wounds to the nervous system

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