細胞の形状と規制モチーフのネガティブリンクは,シグナリングネットワークにおける空間情報フローを共同で制御する
Susana R Neves1, Panayiotis Tsokas, Anamika Sarkar
1Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1215, New York, NY 10029, USA.
Cell
|May 20, 2008
まとめ
細胞の幾何学と制御フィードバックループは,細胞内信号伝播を制御する. フォスファタゼのようなネガティブレギュレータは,マイクロドメインのサイズとニューロン内の情報転送を決定する.
科学分野:
- 細胞生物学 細胞生物学
- バイオフィジックス 生物物理学
- 計算神経科学とは
背景:
- 細胞内信号伝達ネットワークの空間的ダイナミクスは,細胞の機能にとって極めて重要ですが,依然として十分に理解されていません.
- 細胞のサイズと形が信号伝達経路における空間情報の発生と伝播にどのように影響するかは不明である.
研究 の 目的:
- 細胞内信号伝播の制御における細胞幾何学の役割をモデル化し調査する.
- マイクロドメインの空間情報伝達およびシグナル伝達特性に負のレギュレータと反応率が影響するメカニズムを解明する.
主な方法:
- cAMP/PKA/B-Raf/MAPK1,2信号ネットワークにおける空間情報フローをモデル化するために部分微分方程式を用いた.
- リアルなニューロンの幾何学を数値シミュレーションに組み込みました.
- ネズミの海馬のスライスで実験的に検証されたモデル予測.
主要な成果:
- 細胞の形状は,調節ループ内の負の調節物質 (例えば,フォスフォディエステラーゼ,タンパク質フォスファタゼ) の動態を制御することが判明しました.
- これらのレギュレータは,活性化信号構成要素を含むマイクロドメインのサイズを決定します.
- ネガティブレギュレータによる空間情報フローの制御に関するモデルの予測は,実験的に確認されました.
結論:
- 細胞の幾何学,負のフィードバックループ,および反応運動は,細胞内の空間情報伝達を共同で調節する.
- これは,細胞が物理的,生化学的特性を通じてシグナル伝達マイクロドメインの特性を制御する方法のメカニズムを提供します.
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