Abstract
Sleep is a fundamental property conserved across species. The homeostatic induction of sleep indicates the presence of a mechanism that is progressively activated by the awake state and that induces sleep. Several lines of evidence support that such function, namely, sleep need, lies in the neuronal assemblies rather than specific brain regions and circuits. However, the molecular mechanism underlying the dynamics of sleep need is still unclear. This review aims to summarize recent studies mainly in rodents indicating that protein phosphorylation, especially at the synapses, could be the molecular entity associated with sleep need. Genetic studies in rodents have identified a set of kinases that promote sleep. The activity of sleep-promoting kinases appears to be elevated during the awake phase and in sleep deprivation. Furthermore, the proteomic analysis demonstrated that the phosphorylation status of synaptic protein is controlled by the sleep-wake cycle. Therefore, a plausible scenario may be that the awake-dependent activation of kinases modifies the phosphorylation status of synaptic proteins to promote sleep. We also discuss the possible importance of multisite phosphorylation on macromolecular protein complexes to achieve the slow dynamics and physiological functions of sleep in mammals.
Highlights
Sleep is a fundamental property of the central nervous system
Genetic studies indicated that calmodulin-dependent kinase II (CaMKII), SIK3, and Extracellular signal-regulated kinase (ERK) are potent kinases that induce sleep
Phosphoproteomic studies indicated that the sleep-wake cycle dominates the phosphorylation status of synaptic proteins
Summary
Sleep is a fundamental property of the central nervous system. A stereotypical sleep-wake transition occurs from seconds to minutes in which most cortical neural activity changes to the sleep-firing pattern. Neural architectures for achieving sleep-wake transition vary. Even jellyfish with a diffuse nervous system undergoes sleep-wake cycle (Nath et al, 2017), suggesting that sleep is not a specific function of animals with a central nervous system but a function that originated in an early stage of metazoan lineage. Despite such anatomical differences in regulating sleep, the characteristics of sleep dynamics are well conserved throughout the phyla. The baseline daily duration of sleep varied depending on the animal species (Campbell and Tobler, 1984; Siegel, 2005) and even within inbred mice strains (Franken et al, 1999; Diessler et al, 2018): such differences are at least in part genetically inherited, suggesting that there are genetic factors that determine the normal amount of sleep per day
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