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bioRxiv · 10.1101/586701

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

Grubbs, J. J.·Lopes, L. E.·van der Linden, A. M.·Raizen, D. M.
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Abstract

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During C. elegans sleep, energetic stores are allocated to non-neural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores corrects adiposity and sleep defects of kin-29 mutants. kin-29 sleep and energy homeostasis roles map to a small number of sensory neurons that act upstream of fat regulation as well as of central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep.\n\nHighlightsO_LISleep is associated with fat mobilization and low ATP levels\nC_LIO_LIMetabolic regulation of sleep requires the salt-induced kinase (SIK) homolog KIN-29\nC_LIO_LIKIN-29 acts in sensory neurons upstream of sleep-promoting neurons\nC_LIO_LINuclear localization of KIN-29 is required for the metabolic regulation of sleep\nC_LIO_LIA type 2 histone deacetylase acts down stream of KIN-29 in the regulation of sleep.\nC_LIO_LILiberation of energy from fat-storage cells promotes sleep.\nC_LIO_LIBeta-oxidation promotes sleep.\nC_LI

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Grubbs, J. J., Lopes, L. E., van der Linden, A. M., Raizen, D. M.. 2019-03-22. A salt-induced kinase (SIK) is required for the metabolic regulation of sleep. https://doi.org/10.1101/586701

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