期刊
NATURE
卷 539, 期 7629, 页码 378-383出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature20142
关键词
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资金
- World Premier International Research Center Initiative from MEXT
- JSPS KAKENHI [26220207, 16K15187, 26507003, 15K18966, 00635089, 16K18358, 15J06369, 16K18583]
- MEXT KAKENHI [15H05935]
- Welch Foundation [I-1608]
- NIH [GM111367]
- Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST program) from JSPS
- Uehara Memorial Foundation
- Takeda Science Foundation
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Grants-in-Aid for Scientific Research [26870077, 16H04650, 26250024, 16H00590, 16H00588, 26507008, 16K18358, 26507003, 16K18583, 26220207, 15J06369, 16K15187, 15K18966, 15H05935, 26221004] Funding Source: KAKEN
Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively.
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