A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Grubbs, Jeremy J.; Lopes, Lindsey E.; Linden, Alexander M. van der; Raizen, David M.

doi:10.1101/586701

Cited by 7 publications

(8 citation statements)

References 116 publications

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“…Thus, in addition to the ALA neuron that has been long studied in stress-induced sleep [37, 41, 42], the RIS neuron is crucially required for sleep bout induction following cellular stress. This requirement of RIS to induce sleep bouts following cellular stress is consistent with a recent report that used chemogenetic inhibition of RIS[54].…”

Section: Resultssupporting

confidence: 91%

Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress

Konietzka

Fritz

Spiri

et al. 2019

Preprint

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SummarySleep is induced by sleep-active neurons that depolarize at sleep onset to inhibit wake circuits. Sleep-active neurons are under the control of homeostatic and allostatic mechanisms that determine sleep need. However, little is known about the molecular and circuit mechanisms that translate sleep need into the depolarization of sleep-active neurons. During many conditions in C. elegans sleep induction requires a sleep-active neuron called RIS. Here, we defined the transcriptome of RIS to discover that genes of the Epidermal Growth Factor Receptor (EGFR) signaling pathway are expressed in RIS. With cellular stress, EGFR activates RIS, and RIS induces sleep. Activation of EGFR signaling in the ALA neuron has previously been suggested to promote sleep independently of RIS. Unexpectedly, we found that ALA activation promotes RIS depolarization. Our results suggest that ALA is a sedating neuron with two separable functions. (1) It inhibits specific wakefulness behaviors independently of RIS, (2) and it activates RIS to induce sleep. Whereas ALA plays a strong role in surviving cellular stress, surprisingly, RIS does not. In summary, EGFR signaling can induce sleep-active neuron depolarization by an indirect mechanism through activation of the sedating ALA neuron that acts upstream of the sleep-active RIS neuron as well as through a direct mechanism using EGFR signaling in RIS. Sedation rather than sleep appears to be important for increasing survival following cellular stress, suggesting that sedation and sleep play different roles in restoring health.Highlights-The transcriptome of the sleep-active RIS neuron reveals the presence of the EGFR signaling machinery-EGFR activates RIS directly upon cellular stress to induce sleep bouts-In parallel, EGFR activates RIS indirectly through the sedating ALA neuron-Sedation rather than sleep bouts support survival following cellular stress

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Section: Resultssupporting

confidence: 91%

Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress

Konietzka

Fritz

Spiri

et al. 2019

Preprint

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“…A second possible interpretation of PRQ is in terms of energy conservation. C. elegans locomotion requires energy expenditure 61 , and cessation of feeding and activation of DNA repair pathways may contribute to reduced energy stores during UV SIS 62 . Indeed, fat stores decrease during lethargus and ATP levels decrease during lethargus and over the course of UV SIS 62 .…”

Section: Discussionmentioning

confidence: 99%

“…C. elegans locomotion requires energy expenditure 61 , and cessation of feeding and activation of DNA repair pathways may contribute to reduced energy stores during UV SIS 62 . Indeed, fat stores decrease during lethargus and ATP levels decrease during lethargus and over the course of UV SIS 62 . PRQ may allow the animal to compensate for energy depletion associated with an active response with cessation of locomotion and feeding.…”

Section: Discussionmentioning

confidence: 99%

A quiescent state following mild sensory arousal in Caenorhabditis elegans is potentiated by stress

McClanahan

Dubuque

Kontogiorgos-Heintz

et al. 2020

Sci Rep

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“…A second possible interpretation of PRQ is in terms of energy conservation. C. elegans locomotion requires energy expenditure 60 , and cessation of feeding and activation of DNA repair pathways may contribute to reduced energy stores during UV SIS 61 . Indeed, fat stores decrease during lethargus and ATP levels decrease during lethargus and over the course of UV SIS 61 .…”

Section: Discussionmentioning

confidence: 99%

“…C. elegans locomotion requires energy expenditure 60 , and cessation of feeding and activation of DNA repair pathways may contribute to reduced energy stores during UV SIS 61 . Indeed, fat stores decrease during lethargus and ATP levels decrease during lethargus and over the course of UV SIS 61 . PRQ may allow the animal to compensate for energy depletion associated with an active response with cessation of locomotion and feeding.…”

Section: Discussionmentioning

confidence: 99%

A quiescent state following mild sensory arousal inCaenorhabditis elegansis potentiated by stress

McClanahan

Dubuque

Kontogiorgos-Heintz

et al. 2019

Preprint

Self Cite

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In response to threats, animals display quiescent behaviors such as freezing and tonic immobility. How neuromodulatory states like stress affect these behaviors is not well understood. Here we describe a Caenorhabditis elegans quiescent behavior, post-response quiescence (PRQ), which is modulated by the C. elegans response to cellular stressors. Following an aversive mechanical or blue light stimulus, worms respond first by briefly moving, and then become more quiescent for a period lasting tens of seconds. PRQ occurs at low frequency in unstressed animals, but is more frequent in animals that have experienced cellular stress due to ultraviolet light exposure as well as in animals following overexpression of epidermal growth factor (EGF). PRQ requires the function of the carboxypeptidase EGL-21 and the calcium-activated protein for secretion (CAPS) UNC-31, suggesting it has a neuropeptidergic mechanism. Although PRQ requires the sleep-promoting neurons RIS and ALA, it is not accompanied by decreased arousability, and is not homeostatically regulated, suggesting that it is not a sleep state. PRQ represents a simple, tractable model for studying how neuromodulatory states alter behavioral responses to stimuli.

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A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Cited by 7 publications

References 116 publications

Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress

Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress

A quiescent state following mild sensory arousal in Caenorhabditis elegans is potentiated by stress

A quiescent state following mild sensory arousal inCaenorhabditis elegansis potentiated by stress

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