哺乳類の昼夜時計の相互作用する分子ループ
L P Shearman1, S Sriram, D R Weaver
1Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
Science (New York, N.Y.)
|May 12, 2000
まとめ
マウス・マスター・サーカディアン・クロックは,相互作用するフィードバック・ループを使用しています. PERIOD2はBMAL1ループをポジティブに調節し,CRYPTOCHROMESはPeriodとCryptochromeサイクルをネガティブに調節し,重要な分子相互作用を明らかにします.
科学分野:
- クロノバイオロジー クロノバイオロジー
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- マスター・サーカディアン・クロックは,日々の生物学的リズムを調節する.
- 昼間の時計の分子機構を理解することは,クロノバイオロジーにとって極めて重要です.
- 転写と翻訳を含むフィードバックループは,生体時計の既知の構成要素である.
研究 の 目的:
- ネズミの主生時計の核分子のメカニズムを解明する.
- 昼夜リズムを調節する際にPERIOD2とCRYPTOCHROMESの役割を特定する.
- CLOCK:BMAL1とCRYPTOCHROMEタンパク質の相互作用を調査する.
主な方法:
- クロック/クロック変異マウス,Period2(Brdm1) 変異マウス,Cryptochrome欠乏マウスの分析.
- 異なる変異マウスモデルにおけるBmal1リズムの評価.
- CLOCK:BMAL1転写のCRYPTOCHROME阻害を研究するためのインビトロタンパク質:タンパク質相互作用アッセイ.
主要な成果:
- ネズミの昼間時計のコアメカニズムとして,相互に作用する陽性と陰性の転写-翻訳フィードバックループを特定しました.
- Bmal1ループの正規調節におけるPERIOD2の支配的な役割を示した.
- CRYPTOCHROMESは,PERIODと TIMELESSから独立して,直接のタンパク質:タンパク質相互作用を通じて,CLOCK:BMAL1媒介の転写を阻害することを示しました.
- ポジティブなレギュレータとしてPERIOD2と,それぞれのサイクルでネガティブなレギュレータとしてCRYPTOCHROMESを確立しました.
結論:
- マウスの主日時計は,相互接続された正 (PERIOD2) と負 (CRYPTOCHROMES) のフィードバックループを通じて動作します.
- PERIOD2とCRYPTOCHROMESは,コアクロック遺伝子発現とリズムを調節する上で,異なる重要な役割を果たしています.
- 直接のタンパク質相互作用は,CLOCK:BMAL1の転写活動に対するCRYPTOCHROMEの抑制機能を媒介する.
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