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2017 Fiscal Year Annual Research Report

Phosphoproteome of Sleepy brain: probing the mechanism of sleep homeostasis

Research Project

Project/Area Number 16K16639
Research InstitutionUniversity of Tsukuba

Principal Investigator

Wang Zhiqiang  筑波大学, 国際統合睡眠医科学研究機構, 研究員 (00762189)

Project Period (FY) 2016-04-01 – 2018-03-31
Keywordssleep deprivation / Sleepy / sleep need / Slow Wave Activity / Phosphoproteome / SWA / SNIPPs
Outline of Annual Research Achievements

In research period, 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. Thus, phosphorylation/dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis. These results have been accepted by Nature (In press).
The intracerebroventricular (i.c.v.) injection-based and AAV overexpression-based EEG/EMG sleep recording system have been established, we will investigate the function of Sleepy substrates, such as NOS1 through pharmacological and AAV overexpression approaches.

  • Research Products

    (1 results)

All 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Quantitative phosphoproteomic analysis of the molecular substrates of sleep need2018

    • Author(s)
      Zhiqiang Wang, Jing Ma, Chika Miyoshi, Yuxin Li, Makito Sato, etc.
    • Journal Title

      Nature

      Volume: 印刷中 Pages: -

    • Int'l Joint Research

URL: 

Published: 2018-12-17  

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