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- Title
Sleep need, the key regulator of sleep homeostasis, is indicated and controlled by phosphorylation of threonine 221 in salt-inducible kinase 3.
- Authors
Yang Li; Chengang Li; Yuxiang Liu; Jianjun Yu; Jingqun Yang; Yunfeng Cui; Wang, Tao V.; Chaoyi Li; Lifen Jiang; Meilin Song; Yi Rao
- Abstract
Sleep need drives sleep and plays a key role in homeostatic regulation of sleep. So far sleep need can only be inferred by animal behaviors and indicated by electroencephalography (EEG). Here we report that phosphorylation of threonine (T) 221 of the salt-inducible kinase 3 (SIK3) increased the catalytic activity and stability of SIK3. T221 phosphorylation in the mouse brain indicates sleep need: more sleep resulting in less phosphorylation and less sleep more phosphorylation during daily sleep/wake cycle and after sleep deprivation (SD). Sleep need was reduced in SIK3 loss of function (LOF) mutants and by T221 mutation to alanine (T221A). Rebound after SD was also decreased in SIK3 LOF and T221A mutant mice. By contrast, SIK1 and SIK2 do not satisfy criteria to be both an indicator and a controller of sleep need. Our results reveal SIK3-T221 phosphorylation as a chemical modification which indicates and controls sleep need.
- Subjects
HOMEOSTASIS; PROTEIN kinases; SLEEP quality; GENETICS; GENETIC mutation; ELECTROENCEPHALOGRAPHY; THREONINE; ANIMAL experimentation; SLEEP deprivation; RESEARCH funding; GENE expression profiling; PHOSPHORYLATION; MICE
- Publication
Genetics, 2023, Vol 225, Issue 1, p1
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1093/genetics/iyad136