プログラムされた細胞死中にC. elegans CED-4の核膜への転移
1Howard Hughes Medical Institute, Department of Biology, 68-425, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|February 26, 2000
まとめ
C. elegansの細胞死は,CED-9とCED-4タンパク質によって調節される. CED-4はミトコンドリアから核に移動し,細胞死を引き起こし,CED-9がブロックできるプロセスである.
科学分野:
- 細胞生物学 細胞生物学
- 発達生物学 発達生物学とは
- 遺伝学 遺伝学とは
背景:
- プログラムされた細胞死,またはアポトーシスは,発達と組織ホメオスタシスにとって極めて重要です.
- C. elegansでは,Bcl-2-のようなタンパク質であるCED-9は,Apaf-1-のようなタンパク質であるCED-4を反抗することによって,アポトーシスを阻害する.
- CED-4の活動とローカライゼーションを制御する正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- プログラムされた細胞死に関連したCED-4のサブセルラー局在を調査する.
- アポトーシス中のCED-4局所化を調節するCED-9の役割を決定する.
- CED-4転位とカスパース活性化の間の時間的関係を確立する.
主な方法:
- 免疫光顕微鏡で,C. elegans胚のCED-4局所化を視覚化する.
- 野生型,細胞死誘発型,CED-9機能増強型変異胚におけるCED-4局所化の分析.
- ced-3機能に対するCED-4トランスロケーションの依存性の評価.
主要な成果:
- CED-4は,生存可能な野生型の胚のミトコンドリアに局所化している.
- 細胞死を経験している胚では,CED-4が周核部位に転位した.
- EGL-1誘発のCED-4転位は,Ced-9の機能獲得変異によって抑制された.
- CED-4の転位は,ced-3の機能とは独立して発生した.
結論:
- CED-4のサブセルラー局所化は,プログラム細胞死における重要な規制ステップです.
- CED-9は,CED-4の転移を防ぐことで作用する.
- CED-4転位はカスパース活性化に先行し,アポトーシスの開始における初期のイベントであることを示しています.
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