A novel kinase signaling involved in the dual regulation of behavior and metabolism

• Project/Area Number: 25293053
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Nagoya University (2016); Yamaguchi University (2013-2015)
• Principal Investigator: Hayasaka Naoto 名古屋大学, 環境医学研究所, 准教授 (80368290)
• Co-Investigator(Kenkyū-buntansha): 徳田 功 立命館大学, 理工学部, 教授 (00261389) ; 吉岡 芳親 大阪大学, 学内共同利用施設等, 教授 (00174897) ; 西郷 和真 近畿大学, 理工学部, 准教授 (50319688) ; 竹森 洋 国立研究開発法人医薬基盤・健康・栄養研究所, その他部局等, プロジェクトリーダー (90273672) ; 篠田 晃 山口大学, 医学(系)研究科(研究院), 教授 (40192108)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 概日リズム / リン酸化酵素 / 代謝 / ノックアウトマウス / 時計タンパク質 / SIK3 / PER2 / リン酸化 / アストロサイト / タンパク質分解 / Sik3 ノックアウトマウス / 発光イメージング

Outline of Final Research Achievements

Salt-inducible kinase (Sik3) belongs to AMP kinase family known as an "energy sensor", which is involved in the regulation of various aspects of metabolism and osteogenesis. In the present study, we further suggested that SIK3 is also involved in the circadian clock machinery. The knockout study demonstrated that an average free-running period of locomotor activity was significantly longer, and cells and brain slices from knockouts showed unstable circadian rhythms and intercellular desynchrony. We identified PER2 clock protein as a substrate for SIK3, and the PER2 protein was found destabilized by SIK3-mediated phosphorylation.

Research Products

• [Journal Article] A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia (2014)
  • Author(s): Miyoshi, Y., Yoshioka, Y., Suzuki, K., Miyazaki, T., Koura, M., Saigoh, K., Kajimura, N., Monobe,Y., Kusunoki, S., Matsuda, J., Watanabe, M. and Hayakawa, N.
  • Journal Title: PLoS ONE Volume: 9 (9) Issue: 9 Pages: 1-12
  • DOI: 10.1371/journal.pone.0107867
  • Peer Reviewed / Open Access
• [Presentation] Astrocyte as a regulator of the central circadian clock and its input/output pathways (2016)
  • Author(s): Naoto Hayasaka
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] A new understanding of the mammalian circadian clock as neuroglial networks (2015)
  • Author(s): Naoto Hayasaka
  • Organizer: XIV European Biological Rhythms Society Congress
  • Place of Presentation: Mahchester University（イギリス））
  • Year and Date: 2015-08-02
  • Int'l Joint Research / Invited
• [Presentation] Glia makes the clock tick: a role for astrocytes in the circadian rhythm regulation (2015)
  • Author(s): Naoto Hayasaka
  • Organizer: Neuro 2015
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Involvement of astrocytes in the circadian clock machinery (2015)
  • Author(s): Naoto Hayasaka
  • Organizer: Gordon Research Conferences Chronobiology 2015
  • Place of Presentation: PGA Catalunya Business and Convention Centre Girona（スペイン）
  • Year and Date: 2015-06-28
  • Int'l Joint Research / Invited
• [Presentation] 代謝・リズムに共通の制御分子から恒常性維持機構を探る (2015)
  • Author(s): 早坂 直人
  • Organizer: 第120回日本解剖学会総会･全国学術集会・第92回日本生理学会大会合同大会シンポジウム
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Salt-inducible kinase 3 regulates circadian clocks in mice by destabilization of PER2 protein (2014)
  • Author(s): Naoto Hayasaka
  • Organizer: Neuro 2014
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Salt-inducible kinase 3 regulates circadian period and phase by destabilization of PER2 protein (2014)
  • Author(s): Naoto Hayasaka
  • Organizer: SRBR 2014 Meeting (the Society for Research on Biological Rhythms)
  • Place of Presentation: Big Sky Resort（米国、モンタナ州）
  • Year and Date: 2014-06-14 – 2014-06-18
  • Invited
• [Presentation] 新たな概日リズム制御因子Salt-inducible kinase 3 (SIK3) の発見と代謝・概日リズム同時制御の分子基盤の解明 (2014)
  • Author(s): 早坂 直人
  • Organizer: 第119回日本解剖学会総会
  • Place of Presentation: 自治医科大学（栃木県下野市）
• [Presentation] Salt-inducible kinase 3 regulates circadian period and phase by destabilization of PER2 protein (2014)
  • Author(s): 早坂 直人
  • Organizer: SRBR 2014 Meeting (the Society for Research on Biological Rhythms)
  • Place of Presentation: Big Sky Resort（米国、モンタナ州））
• [Presentation] A role for Salt-inducible kinase 3 in the central circadian pacemaker in mammals: phosphorylation-dependent degradation of the clock protein. (2013)
  • Author(s): 早坂 直人
  • Organizer: XIII EBRS Congress (European Biological Rhythm Society)
  • Place of Presentation: ミュンヘン大学（ドイツ）
• [Presentation] A role for Salt-inducibe kinase (SIK3) in the circadian rhythm generation. (2013)
  • Author(s): 早坂 直人
  • Organizer: Neuro 2013
  • Place of Presentation: 京都国際会館（京都市）