AIM2は,細胞プラズマのDNAに反応して,炎症体と細胞死を活性化します
Teresa Fernandes-Alnemri1, Je-Wook Yu, Pinaki Datta
1Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Nature
|January 23, 2009
まとめ
メラノーマ2 (AIM2) に欠けていた炎症ゾームは,細胞質DNAを感知し,カスパース-1とピロプトーシスを活性化します. この発見は,AIM2を明らかにしています.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 宿主または病原体からの細胞質の二重鎖DNAは炎症体を活性化します.
- インフラマソームの活性化は,カスパーゼ-1の活性化とプロインタールイキン-1βの成熟につながります.
- インフラマソームの活性化における細胞質DNAの特定のセンサーは,未確認のままでした.
研究 の 目的:
- 細胞プラズマのDNAが誘発する炎症細胞の活性化に責任のあるセンサータンパク質を特定する.
- 細胞質DNAが炎症体を活性化するメカニズムを解明する.
- インフラマソームとピロプトソーム形成におけるAIM2の役割を特徴づける.
主な方法:
- マクロファージにおけるAIM2発現をノックダウンするために,短い干渉RNA (siRNA) を利用した.
- 細胞質DNAへの反応として,炎症体とピロプトソームの活性化を評価した.
- 反応しない細胞系 (HEK293T) でAIM2を表現して,誘発反応性をテストします.
主要な成果:
- メラノーマ2 (AIM2) の欠席は,細胞質DNAセンサーとして識別されました.
- AIM2のオリゴヌクレオチド/オリゴサカライド結合ドメイン (OB) はDNAを感知し,ピリンドメインはASCと相互作用する.
- AIM2の活性化により,ASCのピロプトソーム形成,カスパーゼ1の活性化,そしてピロプト細胞死が発生する.
結論:
- AIM2は,細胞質DNAを検出する炎症体の重要な構成要素です.
- AIM2のオリゴメリゼーションは,細胞質DNAによって誘発され,炎症ゾームの組み立てを開始します.
- AIM2-ASCの相互作用は,カスパーゼ-1の活性化とピロプトーシスを誘発し,これは重要な先天性免疫反応である.
関連する概念動画
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