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

• Published in: PLoS biology 2020-04, Vol.18 (4), p.e3000220-e3000220
• Main Authors: Grubbs, Jeremy J, Lopes, Lindsey E, van der Linden, Alexander M, Raizen, David M
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adipose tissue; Animals; Animals, Genetically Modified; Authorship; Biology and Life Sciences; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - metabolism; Energy; Energy balance; Energy charge; Energy Metabolism - genetics; Energy storage; Histone deacetylase; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Homeostasis; Homology; Hypotheses; Insects; Kinases; Localization; Mammals; Medicine and Health Sciences; Metabolic regulation; Metabolism; Mutants; Mutation; Neuroendocrine Cells - metabolism; Neurology; Neurons; Nuclei (cytology); Observations; Phosphotransferases; Physical sciences; Physiological aspects; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteins; Research and Analysis Methods; Salt-inducible kinase; Sensory neurons; Sensory Receptor Cells - metabolism; Sleep; Sleep - physiology; Triglycerides
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000220

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During Caenorhabditis elegans sleep, energetic stores are allocated to nonneural 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 set 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.