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Phosphoproteome of Sleepy brain: probing the mechanism of sleep homeostasis

Research Project

Project/Area Number 16K16639
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemical biology
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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordssleep deprivation / Sleepy / sleep need / slow wave activity / phosphoproteome / SNIPPs / Slow Wave Activity / Phosphoproteome / SWA / synaptic proteins / NOS1 / プロテオーム / 睡眠
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 preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation state of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, 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 sleep-wake homeostasis. These results have been accepted by Nature (In press).

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Invited: 1 results) Remarks (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

    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Forward-genetics analysis of sleep in randomly mutagenized mice2016

    • Author(s)
      Funato H and Yanagisawa M et al.
    • Journal Title

      Nature

      Volume: 539(7629) Issue: 46 Pages: 378-383

    • DOI

      10.1038/nature20142

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Synaptic phosphoproteome as a molecular correlate of sleep need2016

    • Author(s)
      Wang Zhiqiang
    • Organizer
      The 5th Annual IIIS Symposium・The 32nd Wako Workshop・Joint Meeting
    • Place of Presentation
      Tokyo Conference Center Shinagawa Minato-ku Tokyo, Japan
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] Solving the mystery of sleep

    • URL

      http://wpi-iiis.tsukuba.ac.jp/wp-content/uploads/2016/12/IIIS-Wako-Abstracts.pdf

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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