NFATの活性化のためのsiRNAスクリーンは,セプチンを,貯蔵されたCa2+のエントリのコーディネーターとして識別します
Sonia Sharma1, Ariel Quintana, Gregory M Findlay
1La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Nature
|June 25, 2013
まとめ
セプチンタンパク質は,STIM1-ORAI1経路を調節することによって,細胞カルシウムシグナル伝達を組織します. これらの発見はセプティンを明らかにしています.
科学分野:
- 細胞生物学 細胞生物学
- 分子シグナリング
- バイオケミストリー バイオケミストリー
背景:
- STIM1-ORAI1経路は,細胞のカルシウム (Ca2+) 信号伝達に不可欠であり,細胞へのCa2+の侵入を制御します.
- STIM1タンパク質はCa2+貯蔵庫の枯渇を感知し,ORAI1チャネルをプラズマ膜に勧誘する.
- Ca2+シグナリングの調節不全は,様々な疾患に絡み合っている.
研究 の 目的:
- STIM1-ORAI1経路の新たなレギュレータを特定する.
- 蓄積されたカルシウムの輸入における有糸状セプチンタンパク質の役割を調査する.
- セプティンがSTIM1-ORAI1複合体の形成に影響を与えるメカニズムを解明する.
主な方法:
- HeLa細胞における全ゲノムRNA干渉 (RNAi) スクリーン.
- STIM1とORAI1のダイナミクスを観察するための生細胞イメージング.
- フォスファディチルイノシトール-4,5-ビスホスファート (PtdIns(4,5) P2) の局所化の分析.
- タンパク質と細胞の構造の相互作用を研究するための顕微鏡技術.
主要な成果:
- 線維性セプチンタンパク質は,貯蔵されたカルシウム入力の重要なレギュレータとして特定されました.
- セプチンフィラメントとPtdIns ((4,5) P2は,STIM1-ORAI1のクラスタリング中に,エンドプラズマ網膜-プラズマ膜の交差点で再編成する.
- セプティンの再配置は,STIM1のターゲティングと安定したORAI1の採用を促進し,STIM1-ORAI1のコミュニケーションを強化します.
- セプティンは,STIM1-ORAI1シグナル伝達に不可欠な局所化されたプラズマ膜ドメインを組織します.
結論:
- セプティンは,効率的なSTIM1-ORAI1カルシウムシグナル伝達に必要な局所的な膜ドメインの組織化において重要な役割を果たします.
- セプティンは,さまざまな細胞プロセスにおけるシグナル伝達マイクロドメインを組織するための支架として機能する可能性があります.
- この研究は,セプチンの既知の機能を拡張し,貯蔵されたカルシウム入力の調節を含む.
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