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NINJ1は,溶解細胞死中の血破裂を媒介する.

  • 0Department of Physiological Chemistry, Genentech Inc., South San Francisco, CA, USA. kayagaki@gene.com.
Nature +

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2021年1月20日

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2021年1月20日

PubMedで要約を見る

まとめ

この要約は機械生成です。

NINJ1タンパク質は血破裂 (PMR) に欠かせないもので,これは溶解性細胞死における重要な出来事である. この発見は,NINJ1

科学分野

  • 細胞生物学
  • 免疫学
  • 遺伝学

背景

  • プラズマ膜破裂 (PMR) は,炎症を誘発するダメージ関連分子パターン (DAMP) を放出する,リティック細胞死における末期的な出来事である.
  • PMRを制御する分子メカニズムはほとんど不明のままです.
  • NINJ1タンパク質は,細胞表面に2つのトランスメブラン領域があるが,細胞死におけるその機能は不明であった.

研究 の 目的

  • 溶解性細胞死におけるプラズマ膜破裂 (PMR) の根本的なメカニズムを解明する.
  • PMRのプロセスに関与する重要な分子プレーヤーを特定する.
  • PMRにおけるNINJ1タンパク質の役割とその宿主防御への貢献を調査する.

主な方法

  • PMRを調節する遺伝子を特定するために,ランダムに変異したマウスの遺伝子スクリーニングを進める.
  • Ninj1ノックアウト (Ninj1-/-) マクロファージとマウスの分析
  • HMGB1 と LDH のような細胞内タンパク質の放出を測定することによって,PMRの評価.
  • 細胞死を観察するための顕微鏡検査.
  • 宿主防御を評価するためにCitrobacter rodentiumを用いた感染研究

主要な成果

  • NINJ1タンパク質は,PMRの重要なメディエーターとして特定されました.
  • 細胞死 (ピロプトーシス,ネクロシス,アポプトーシス) の様々な経路において,ニンジ1- / - マクロファージはPMRの障害を示した.
  • Ninj1- / - マクロファージは,持続的な風船形状の細胞分解を示した.
  • Ninj1- / - マウスはCitrobacter rodentiumの感染に対する感受性の増加を示し,抗菌防御におけるPMRの役割を示した.
  • NINJ1は細胞外ドメインのオリゴメリゼーションによってPMRを誘発する.

結論

  • NINJ1は,プラズマ膜破裂 (PMR) の重要な進化的に保存された媒介体である.
  • NINJ1の役割の発見は,PMRが受動的な細胞現象であるという長年の見解に異議を唱える.
  • NINJ1媒介のPMRは,宿主の抗菌防御に重要な役割を果たします.

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