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Lynはリドックスセンサーで,白血球の傷の引き寄せを vivo で媒介する
Sa Kan Yoo1, Taylor W Starnes, Qing Deng
1Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Nature
|November 22, 2011
まとめ
科学者は,Srcファミリーキナーゼ (SFK) Lynが酸化還元センサーとして作用することを発見しました. このセンサーは,傷部位で過酸化水素 (H2O2) を検出し,中性粒子の受傷組織への募集を媒介します.
科学分野:
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
- バイオケミストリー バイオケミストリー
背景:
- 傷ついた組織への白血球の徴募は,急速なプロセスです.
- NADPH酸化酵素 (NOX) によって生成される過酸化水素 (H2O2) は,白血球の傷や腫瘍への募集を媒介する.
- 中性粒子が傷口での酸化還元状態を検出するために使用する特定のセンサーは,未確認のままです.
研究 の 目的:
- 傷の部位への中性粒子の徴集を担当するセンサーを特定する.
- 中性粒子が損傷部位における酸化還元変化を検出するメカニズムを解明する.
主な方法:
- 組織損傷と中性粒子の募集のインビボモデルとしてゼブラフィッシュの幼虫を使用した.
- Lynの機能を研究するために遺伝子操作 (トランス遺伝子組織特異的再構成) を採用した.
- Lyn活性化に関与する特定のシステイン残留物を特定するために,in vitro生化学的測定を行った.
主要な成果:
- Srcファミリーキナーゼ (SFK) Lynを,ゼブラフィッシュの傷口への中性粒子の募集を媒介する酸化還元センサーとして特定しました.
- Lynの活性化は,傷から派生するH2O2に依存し,Lynの阻害は中性粒子の募集を弱めることを示した.
- 酸化媒介によるリン活性化と中性粒子の化学毒作用において,システイン残留物466 (C466) を決定的に重要視した.
結論:
- Lynは生理学的リドックスセンサーとして機能し,傷口の部位でH2O2を直接検出します.
- Lyn C466は,中性粒子の募集と,組織損傷への反応として下流シグナル伝達に不可欠です.
- この研究は,多細胞生物における白血球の傷の引き寄せを媒介するリドックスセンサーの最初の識別を表しています.
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