ESCRTに依存する膜修復は,GSDMDの活性化の後流のピロプトーシスを否定的に制御する

Sebastian Rühl^1,2, Kateryna Shkarina³, Benjamin Demarco³

¹Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.

Science (New York, N.Y.)

|November 24, 2018

まとめ

ESCRT-III機構を伴う細胞膜修復は,熱死と炎症を抑制する. この過程はガスダーミンDの毛穴を通るカルシウム流入によって引き起こされ,細胞生存に関する洞察を与えます.

科学分野:

細胞生物学
免疫学
細胞死の分子機構

背景:

ピロプトーシスは炎症性プログラム細胞死経路で,炎症体によって活性化されます.
炎症性カスパスはガスダーミンD (GSDMD) を割って,ピロプトーシスを実行する毛穴を形成する.

研究の目的:

ピロプトーシスにおける細胞修復メカニズムの役割を調査する.
膜の修復が炎症の程度と関連する炎症に影響するかどうかを判断する.

主な方法:

人間とネズミの細胞における正規および非正規の炎症体経路の活性化.
GSDMDの毛穴を通るカルシウム流入の分析
ESCRT-IIIの機械の採用と機能の評価
ピロプトーシスとIL- 1βの放出に対する影響を評価するためにESCRT- IIIの抑制.

主要な成果:

ESCRT媒介の膜修復のためのGSDMDの毛孔信号を通じたカルシウム流入.
ESCRT-IIIの機械は GSDMDによる膜損傷に採用されています.
ESCRT-IIIの抑制は,ピロプトーシスとIL- 1βの放出を著しく強化する.

結論:

ESCRT-IIIシステムは,炎症性膜の毛穴を修復することで,重要な抗炎症的役割を果たします.
細胞膜の修復メカニズムは,熱死とその炎症的結果を制限するために不可欠です.
発見は,ピロプトーシス中の細胞生存戦略の洞察を提供します.

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