アクチン細胞骨格再構成プライム RIG-I型受容体活性化
Dhiraj Acharya1, Rebecca Reis2, Meta Volcic3
1Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA; Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
Cell
|September 16, 2022
まとめ
アクチン細胞骨格の乱れは,先天的な免疫のためのRNA感知経路を原始化します. この発見は,抗ウイルス防御のための新しいメカニズムを明らかにし,インターフェロン反応とウイルス感染に対する感受性に影響を与えています.
科学分野:
- 免疫学
- 細胞生物学
- ウイルス学
背景:
- 生まれつきの免疫は,インターフェロン反応を活性化するために,RNAリガンドを感知することに依存しています.
- これらのRNAセンサを起動する正確なメカニズムは まだ完全に理解されていません
研究 の 目的:
- 生まれながらの免疫におけるRIG-I型受容体 (RLR) の活性化に起因する新たな要因を調査する.
- RLRシグナル伝達におけるアクチン細胞骨格の役割を明らかにする.
主な方法:
- RLRの活性化に対するアクチン細胞骨格の障害の影響を研究した.
- ウイルスの感染とRNAの配送中にPPP1R12Cの移転を調査した.
- 抗ウイルス反応におけるその役割を評価するために,PPP1R12Cの遺伝子切除を用いた.
主要な成果:
- ウイルス感染またはRNA配送反応剤によって誘発されたアクチン細胞骨格の乱れは,RLRの活性化を促します.
- PPP1R12Cは,タンパク質フォスファタゼ-1の調節子単位であり,アクチン破壊時に細胞質RLRに移行する.
- PPP1R12Cによって媒介される脱酸化は,効率的な下流シグナル伝達に不可欠なRLRプライミングを可能にします.
- PPP1R12Cの遺伝子消去は抗ウイルス免疫を弱め,SARS-CoV-2やインフルエンザのようなRNAウイルスに対する感受性を高めます.
結論:
- アクチン細胞骨格の乱れは,RLR媒介の先天性免疫のための重要なプライミング信号として作用する.
- PPP1R12Cは,アクチンダイナミクスをRLRプライミングと結びつける重要なメディエーターとして特定されています.
- この発見は抗ウイルス薬と補助剤の開発の新たな戦略を提示しています.
関連する概念動画
Mechanism of Filopodia Formation
2.4K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
Mechanism of Lamellipodia Formation
2.7K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.7K
IP3/DAG Signaling Pathway
12.3K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.3K
Generation of Straight or Branched Actin Filaments
3.0K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.0K


