関連する実験動画

Updated: Apr 10, 2026

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

STINGは,周期的なdi-GMPの直接的な先天性免疫センサーです

Dara L Burdette¹, Kathryn M Monroe, Katia Sotelo-Troha

¹Department of Molecular & Cell Biology, University of California, Berkeley, California 94720, USA.

|September 28, 2011

まとめ

IFN遺伝子の刺激タンパク質 (STING) は,細菌の重要なシグナル伝達分子である周期性ダイヌクレオチドを直接感知する. この発見は,STINGを明らかにしています.

科学分野:

生まれながらの免疫力があります.
分子免疫学分子免疫学
シグナルトランスデュークション.

背景:

生まれながらの免疫系は,生殖系にコード化された受容体を用いて,保存された微生物の分子を検出し,病原体の除去に不可欠なタイプIインターフェロン (IFN) のようなサイトカインの産生を誘発する.
細胞塩基DNA検出は,タンク結合キナーゼ1 (TBK1) とIFN調節因子3 (IRF3) を通してIFN生成を誘導する.
STING (IFN遺伝子の刺激器) は,信号アダプタとして作用し,細胞塩基DNA検出をTBK1-IRF3経路とリンクする. 周期性ダイヌクレオチドもSTING依存のIFN応答を誘発するが,そのセンサーは不明であった.

研究の目的:

サイクリック・ディヌクレオチドの哺乳類センサーを識別する.
生まれながらの免疫応答における周期性ダイヌクレオチド認識のメカニズムを解明する.
サイクリック・ディヌクレオチドの文脈におけるシグナル・アダプタを超えたSTINGの役割を調査する.

主な方法:

STINGの相互作用を評価するために,放射性マーキングされた循環型ディガニラートモノフォスファート (c-di-GMP) を使用した拘束性アッセイ.
コンペティションは,結合特異性を決定するために,様々なヌクレオチドと核酸を用いた測定法を行います.
STINGの突然変異は,DNA応答とは独立して周期性ダイヌクレオチド応答に影響を与える変異を特定するために.

主要な成果:

STINGは,周期性ダイヌクレオチド,特にc-di-GMPに直接結合する.
標識されていないサイクリック・ディヌクレオチドは,他のヌクレオチドや核酸は含まないが,STING結合に競争した.
STINGの変異は,DNAへの反応を保ちながら,周期性ダイヌクレオチドに対する反応を選択的に損なうと特定されました.

結論:

STINGは,循環性ダイヌクレオチドの直接的な先天性免疫センサーとして機能し,また,細胞性DNAのシグナルアダプタとしての役割も果たしています.
この発見は,バクテリア由来の循環型ジヌクレオチドが宿主の先天性免疫システムによってどのように感知されるかについてのメカニズム的な洞察を提供します.
センサとアダプタとしてのSTINGの二重の役割を理解することは,ワクチン補助剤と免疫療法薬としての循環性ダイヌクレオチドの開発に意味があります.

さらに関連する動画

Capture Compound Mass Spectrometry - A Powerful Tool to Identify Novel c-di-GMP Effector Proteins

Capture Compound Mass Spectrometry - A Powerful Tool to Identify Novel c-di-GMP Effector Proteins

Published on: March 29, 2015

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Published on: June 30, 2016

関連する概念動画

Intracellular Signaling Cascades

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...

Amplifying Signals via Second Messengers

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...

Activation and Inactivation of G Proteins

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...

GPCRs Regulate Adenylyl Cylase Activity

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...

IP3/DAG Signaling Pathway

IP3/DAG Signaling Pathway

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...

Calmodulin-dependent Signaling

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...