日常の肝臓リズム:形態学的および分子的な振動を組み合わせる
Ueli Schibler1, Flore Sinturel2, Felix Naef3
1Department of Molecular and Cellular Biology, Sciences III, Geneva CH-1205, Switzerland.
まとめ
肝臓
科学分野:
- クロノバイオロジー
- 分子生物学
- ヘパトロジー
背景:
- 哺乳類の生理は,階層的な昼夜時計システムによって支配され,上皮神経核 (SCN) がマスターペースメーカーである.
- 代謝適応に不可欠な肝臓は 遺伝子発現,タンパク質合成,解毒の毎日のリズムを示しています
- 肝臓の質量と肝細胞の形状は 24時間間で大きく変動します
研究 の 目的:
- 肝臓の質量と肝細胞の大きさの昼間振動の背後にあるメカニズムを調査する.
- これらの昼夜リズムを調節するアクチン細胞骨格と関連するシグナル伝達経路の役割を調査する.
- これらの細胞の変化が 肝臓の時計の同期に 寄与する仕組みを理解するためです
主な方法:
- 肝臓の質量,肝細胞のサイズ,RNA,タンパク質の蓄積の毎日の変動を研究するためにマウスモデルを使用した.
- リボソームの含有量とタンパク質合成率との相関を分析した.
- アクチン細胞骨格の動態と,ミオカルディン関連の転写因子-血清応答因子 (MRTF-SRF) 信号によるその調節を調査した.
主要な成果:
- ネズミの肝臓の質量は毎日30~40%変動し,肝細胞のサイズと全体的なタンパク質/RNA濃度のリズム的な変化が伴います.
- リボソームの多さは肝臓のサイズと相関し,昼間のタンパク質合成の速度を制限する要因として作用する.
- 肝細胞のアクチン細胞骨格は,肝臓の最大サイズに一致する夜間にF-アクチンの束が組み立てられ,重要なポリメリゼーションサイクルを経験します.
結論:
- 肝臓の循環リズムは,肝細胞のサイズとリボソームの含有量の振動によって引き起こされ,タンパク質合成に影響します.
- 肝細胞におけるアクチンポリメリゼーションサイクルは,サイズ変動中に細胞の強さを維持するために不可欠です.
- アクチンダイナミクスの影響を受けたMRTF-SRFシグナリングは,PER2のような時計遺伝子の昼夜転写に役割を果たし,肝臓の時計を同期します.
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