Exploration and analysis of novel components of intracellular molecular cascade for sleep

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21206
• Project/Area Number (Other): 18H06083 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Kitazono Tomohiro 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (40826517)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 睡眠 / 覚醒 / シグナル伝達経路 / キナーゼ / スクリーニング / パスウェイ解析 / リン酸化

Outline of Final Research Achievements

We recently reported that single nucleotide substitution (Sleepy mutation) in serine/threonine kinase SIK3 caused dramatically prolonged sleep time (Funato et al, 2016), and increase of sleep need broadly induced cumulative phosphorylation of the brain proteome (Wang et al, 2018). These results suggested that sleep need was regulated by unknown intracellular signaling pathways, in which serine/threonine kinase SIK3 functioned. To reveal these signaling pathways, we explored the novel substrate of SIK3. To identify the novel SIK3 substrate, we conducted in vitro substrate screening, KIOSS (Kinase-Oriented Substrate Screening) (Nishioka et al., 2015), and newly identified 56 phosphorylation sites in 38 proteins as the candidates of SIK3 phosphorylation sites. Furthermore, we performed pathway analysis with these candidate proteins, and found one signaling pathway, which possibly functioned downstream of SIK3.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

睡眠は、記憶形成、感情調節、代謝、発達、老化といった様々な生命機構と関連している。本研究で新規に同定した新規分子の知見をもとに、睡眠覚醒を制御する細胞内分子機構を明らかにすることで、生命科学における幅広い分野の研究の発展に寄与することが期待される。また、不眠は鬱病などの気分障害やメタボリック症候群などの様々な疾患のリスクを高めることも知られている。本研究で得られた知見をもとに、睡眠障害の治療薬開発の標的分子を明らかすることは、睡眠障害と関連する疾患の治療の進歩におおいに貢献できる。