| Project/Area Number |
17K15592
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Ma Jing 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (70793222)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Sleepy / sleep need / sleep / SNIPPs / single prolonged stress / mPFC / PTSD / immunoprecipitation / mass spectrometric / sleep/wakefulness / signal transduction / protein kinase / phosphoproteome / 睡眠覚醒 / 細胞内シグナル伝達系 / リン酸化酵素 |
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| Outline of Final Research Achievements |
We performed quantitative phosphoproteomic studies of whole mouse brains from two models of sleep/wake perturbation. A combined proteome and phosphoproteome data for 9,410 mouse proteins and 62,384 phosphopeptides were examined. Comparison of two models identifies 80 mostly synaptic Sleep-Need-Index-PhosphoProteins (SNIPPs), whose phosphorylation states closely parallel changes of sleep need. Mutant SLEEPY/SIK3 kinase preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation state of SNIPPs and slow wave activity (SWA) during non-rapid-eye-movement sleep (NREMS), the best known measurable index of sleep need, in both Sleepy and sleep-deprived wild-type mice. Our results suggest that SNIPPs accumulate/dissipate phosphorylation as the molecular substrate of sleep need.
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| Academic Significance and Societal Importance of the Research Achievements |
For the first time, our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and the phosphorylation dephosphorylation cycle of SNIPPs represent a major regulatory mechanism underlies sleep wake homeostasis.
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