Bcl-x(L) は,合成脂質膜のイオンチャネルを形成する

A J Minn¹, P Vélez, S L Schendel

¹Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Illinois 60637, USA.

Nature

|January 23, 1997

まとめ

アンチアポトーシスタンパク質Bcl-xLは細胞膜にイオンチャネルを形成する. この発見は,Bcl-xLが膜の透過性を制御することによって細胞生存を調節することを示唆しています.

科学分野:

バイオケミストリーバイオケミストリー
分子生物学は分子生物学である.
細胞生物学細胞生物学

背景:

Bcl-2に関連するタンパク質は細胞生存を調節し,重要な細胞内膜に存在します.
Bcl-xLを含むこれらのタンパク質の正確な生化学的機能は完全に理解されていません.
Bcl-xLはアポトーシスの阻害剤として知られています.

研究の目的:

Bcl-xL.L.の生化学的機能を調査する.
孔を形成する細菌の毒素のように,Bcl-xLがイオンチャネルを形成できるかどうかを判断する.
膜透過性による細胞生存の調節におけるBcl-xLの役割を明らかにする.

主な方法:

Bcl-xLと孔を形成する細菌毒素の構造的比較.
合成脂質ベジクルと平らな脂質二層を用いた機能分析.
イオンチャネル活動を特徴付けるための電気生理学的測定.

主要な成果:

Bcl-xLは,細菌の毒素の毛穴形成ドメインと構造的に類似していることが示されました.
Bcl-xLは,脂質二重層にうまく挿入され,イオン伝導チャネルを形成しました.
Bcl-xLイオンチャネルは,複数の導電性状態で,生理的なpHでpH感度とcation選択性を示した.

結論:

Bcl-xLは,バクテリア毒素と同様のイオンチャネル形成能力を有しています.
Bcl-xLによるイオンチャネルの形成は,細胞生存を調節する新しいメカニズムを示唆しています.
Bcl-xLは,ミトコンドリア,核,エンドプラズマ網膜の浸透性を調節することにより,細胞生存を制御する可能性があります.

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