Understanding molecular basis of homeostatic maintenance by SIK3, a regulator common to circadian rhythm, sleep and metabolism
| Project/Area Number |
18K06334
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
|
|---|
| Research Institution | Nagasaki University (2020)
Nagoya University (2018-2019) |
|---|
Principal Investigator |
HAYASAKA Naoto 長崎大学, 医歯薬学総合研究科(歯学系), 客員研究員 (80368290)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | SIK3 / PER2 / ケモカイン / オートファジー / 概日時計 / 睡眠 / 遺伝子ノックアウト / リン酸化酵素 / 代謝 / 共通制御 / リン酸化シグナル / ノックアウトマウス / リン酸化基質 / ウイルスベクター |
|---|
| Outline of Final Research Achievements |
This study aimed that 1) analysis of the degradation mechanism of PER2 by SIK3, 2) identification of new SIK3 substrates involved in the regulation of circadian rhythm, sleep, and metabolism, and 3) elucidation of whether circadian clock is involved in the regulation of sleep and metabolism via SIK3 signaling.
Our data suggest that autophagy is involved in the degradation pathway of PER2. We also identified a chemokine receptor as a candidate SIK3 substrate. Abnormal circadian activity rhythms were observed in both of the chemokine receptor and its ligand KO mice, suggesting that regulation of circadian rhythm by SIK3 is mediated by the chemokine signaling. In addition, our results suggest that SIK3 is also involved in sleep regulation, at least in part, through the chemokine and its receptor.
|
| Academic Significance and Societal Importance of the Research Achievements |
体内時計は生物の活動や生理現象を制御し、恒常性維持に重要な役割を果たすが、体内時計が行動や多様な生理現象を制御する共通のメカニズムの存在については、未解明であった。本研究では、進化の過程で下等動物から哺乳類まで保存されてきたSIK3というリン酸化酵素が、体内時計に関わる複数の新たに同定されたタンパク質の制御を介して恒常性の維持に重要な役割を果たしていることが示唆された。
本研究は、常に変動する環境の中で生体内の安定性を維持する仕組みである恒常性における体内時計の重要性をより明らかにし、恒常性維持機構の破綻ともいえる疾患の研究に体内時計という視点が不可欠であることを強く示唆するものであるといえる。
|
Report
(4 results)
Research Products
(3 results)
