LRRC26補助タンパク質は,カルシウムなしで静止電圧でBKチャネル活性化を可能にします
Jiusheng Yan1, Richard W Aldrich
1Section of Neurobiology, Center for Learning and Memory, University of Texas, Austin, Texas 78712, USA.
Nature
|July 9, 2010
まとめ
興奮不可能な細胞内の大導電性カリウム (BK) チャンネルは,LRRC26.6によって活性化されます. この補助タンパク質は,膜脱極化とは関係なく,生理的な電圧とカルシウムレベルでのBKチャネル機能を可能にします.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生理学 細胞生理学
- イオンチャネル機能
背景:
- 大伝導性,電圧,およびカルシウム活性化カリウム (BK) チャンネルは,細胞興奮性において極めて重要です.
- BKチャネルは,活性化には通常,膜脱極化と細胞塩酸カルシウム濃度の上昇が必要で,この条件はほとんどの非刺激性細胞では満たされない.
- 興奮不能の細胞におけるBKチャネルゲーティングを調節する補助サブユニットの役割は,まだ完全に理解されていません.
研究 の 目的:
- 非刺激性LNCaP前立腺がん細胞におけるBKチャネル活性化のメカニズムを調査する.
- 非刺激性細胞の生理学的条件下でBKチャネル活性を与える補助タンパク質を特定する.
- 補助タンパク質によるBKチャネルゲーティング調節の分子基礎を解明する.
主な方法:
- LNCaP細胞における電気生理学的記録.
- 相互作用するタンパク質を識別するための共免疫プレシピテーション.
- タンパク質の相互作用と機能的効果を調査するためのサイト指向型変異.
- BKチャネルゲーティング特性を判断するための電圧クランプ分析.
主要な成果:
- LNCaP細胞のBKチャネルは,細胞塩酸カルシウムの増加なしに,負の膜ポテンシャルで活性化することができます.
- レウシンに富んだリピート含有タンパク質26 (LRRC26) は,これらの細胞のBKチャネルと複合体を形成します.
- LRRC26は,BKチャネル活性化の電圧依存を,より負のポテンシャル (約. -140 mV) である.
- LRRC26は,電圧センサーの動きとチャネルの開口との間のアロステリックカップリングを強化します.
結論:
- LRRC26は,BKチャネルのための新しい補助サブユニットとして作用し,興奮不可能な細胞での機能を可能にします.
- LRRC26-BKチャネル複合体は,生理学的電圧とカルシウムレベルでの活性化を可能にします.
- この発見は,興奮不可能な細胞タイプにおけるBKチャネル活性に対する分子的な説明を提供し,細胞信号伝達の理解に影響を与えています.
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