LDL受容体に関連するタンパク質LRP6は,炭毒素の内部化と致死性を媒介する
Wensheng Wei1, Quan Lu, G Jilani Chaudry
1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|March 28, 2006
まとめ
低密度リポプロテイン受容体関連タンパク質6 (LRP6) は,炭毒素が哺乳類の細胞に侵入するのに不可欠です. LRP6を阻害すると,毒素の内部化が防止され,細胞が致死的な影響から保護され,炭菌対策の新たな標的が明らかになる.
科学分野:
- 細胞生物学 細胞生物学
- 微生物学 微生物学とは
- 免疫学 免疫学とは
背景:
- Bacillus anthracisを含む微生物の毒素は,その毒性の作用のために宿主細胞の遺伝子機能を必要とします.
- Wnt信号伝達経路は,低密度リポプロテイン受容体関連タンパク質6 (LRP6) をコアセプターとして利用しています.
研究 の 目的:
- 哺乳類の細胞における炭毒素の致死性におけるLRP6の役割を調査する.
- 炭菌毒素に対する対抗策を開発するための潜在的な新たな標的を特定する.
主な方法:
- LRP6発現のダウンレギュレーションと支配的ネガティブなペプチドの使用.
- LRP6の細胞外エピトープを標的にする抗体媒介阻害.
- 光顕微鏡検査と生化学分析により,毒素の内部化を研究する.
- LRP6,保護性抗原 (PA) 受容体 (TEM8/ATR,CMG2) と炭毒素との相互作用を調査する.
主要な成果:
- LRP6は,哺乳類の細胞における炭毒素の致死性のために必要である.
- LRP6の機能を抑制 (ダウンレギュレーション,ドメインネガティブペプチド,または抗体経由) は,炭毒素の保護性抗原 (PA) の細胞吸収を阻害した.
- LRP6は,細胞表面にPA受容体 (TEM8/ATRおよび/またはCMG2) と複合体を形成することで,PAの結合と侵入を可能にすることで,毒素の内部化を促進します.
- この相互作用は,LRP6の毒素の侵入におけるこれまで未知の機能を明らかにしています.
結論:
- 低密度リポプロテイン受容体関連タンパク質6 (LRP6) は,宿主細胞への炭毒素の侵入を媒介する上で,これまで認識されていない重要な役割を果たしています.
- LRP6の機能は,PA受容体との相互作用を通じて毒素の内化を促進し,新しい炭菌対策の開発のための有望な治療標的として識別します.
さらに関連する動画
08:24Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
09:30Analyzing Dynamic Protein Complexes Assembled On and Released From Biolayer Interferometry Biosensor Using Mass Spectrometry and Electron Microscopy
Published on: August 6, 2018
関連する概念動画
01:38Receptor-mediated Endocytosis
Overview
01:20Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:36Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
01:19Formation of Lipopolysaccharides
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
01:25Inhalation Anthrax
Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or...