Phosphoproteome of Sleepy brain: probing the mechanism of sleep homeostasis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K16639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: University 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
• Keywords: sleep deprivation / Sleepy / sleep need / slow wave activity / phosphoproteome / SNIPPs

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).

Free Research Field

複合領域