ブレフェルディンAの作用は, pertussis-toxinに敏感なGタンパク質の活性化によってブロックされます
N T Ktistakis1, M E Linder, M G Roth
1Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas 75235-9038.
Nature
|March 26, 1992
まとめ
特定のGタンパク質は,コートタンパク質がゴルギ膜に結合する方法を調節する. この発見は,ブレフェルディンAを理解するのに役立ちます.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ブレフェルディンAは,哺乳類の細胞におけるゴルギ装置とエンドプラズマ網膜の分離を妨害する.
- 最も早く観察された効果は,ゴルギからβ-COPコートタンパク質の放出である.
- GTP-gamma SまたはAlF4-の前処理は,このβ-COPの放出を阻害し,Gタンパク質の関与を示唆する.
研究 の 目的:
- ゴルギ膜とコートタンパク質の結合を調節するヘトロトリメリックGタンパク質の役割を調査する.
- 特定のGタンパク質サブファミリーがERとGolgiの間の膜移転を制御するかどうかを判断する.
主な方法:
- ヘテロトリメリックGタンパク質のペプチド活性化剤であるマストパランを使用した.
- Golgi膜へのβ-COP結合を in vitroで評価した.
- 穿孔した細胞と孤立したゴルギ膜におけるβ-COPに対するブレフェルディンAの効果を調べた.
- これらの相互作用に対する pertussis toxin 前治療の影響を調査しました.
主要な成果:
- マストパランは,試験管内で Golgi 膜へのβ-COP 結合を促進した.
- マストパランは,細胞系と隔離膜系の両方で,β-COPに対するブレフェルジンAの効果を逆転させた.
- 百日咳毒素の前治療は,マストパランのブレフェルディンAに対する抑制効果を著しく低下させた.
結論:
- ゲトロトリメリックなGタンパク質は,おそらくGi/Goサブファミリーに属し,コートタンパク質とゴルギ膜の結合を調節する.
- このGタンパク質は,ゴルギ-ER分離を維持する上で重要な役割を果たします.
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