ラグレーター-ラグ-mTORC1経路によるガスダーミンDのオリゴメリゼーションとピロプトーシスの制御
Charles L Evavold1, Iva Hafner-Bratkovič2, Pascal Devant1
1Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell
|July 21, 2021
まとめ
ラグレーター-ラグ複合体は,細胞死プロセスである熱死期におけるガスダーミンD (GSDMD) の毛穴形成に不可欠である. この発見は免疫調節と 細胞代謝を結びつけています
科学分野:
- 免疫学
- 細胞生物学
- 分子生物学
背景:
- ピロプトーシスは 免疫に不可欠な プログラムされた細胞死経路です
- インフラマソームとガスダーミンD (GSDMD) は熱死の主な媒介体である.
- GSDMDの裂け方はよく研究されているが,下流の毛穴形成のメカニズムは不明である.
研究 の 目的:
- ガスダーミンD (GSDMD) の毛穴形成に必要な新しいタンパク質を特定する.
- GSDMD媒介の熱殺を制御する分子機構を明らかにする.
主な方法:
- マクロファージの遺伝子スクリーニング
- GSDMDの裂け方,オリゴメリゼーション,および毛穴形成を評価するための生化学的測定法.
- 反応性酸素種 (ROS) 生産の分析
主要な成果:
- ラグレーター-ラグ複合体は,GSDMDの毛穴形成と熱死に不可欠であると特定されました.
- ラグレーター- ラグはGSDMDの分裂には関わらないが,プラズマ膜でのオリゴメリゼーションを促進する.
- 反応性酸素種 (ROS) を増やすミトコンドリア毒は,GSDMDの毛穴形成の欠陥を救済することができます.
結論:
- ラグレーター-ラグ複合体は,GSDMDの毛穴形成において,これまで認識されていない重要な役割を果たしています.
- 反応性酸素種 (ROS) は,GSDMDの孔集の重要なレギュレーターである.
- この研究は免疫信号伝達経路と 代謝調節の間の新しい関連性を明らかにしています
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