細胞外プロテオスタシスは,病原性の攻撃中に集積を防ぐ
Ivan Gallotta1, Aneet Sandhu1,2, Maximilian Peters3
1German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Nature
|July 10, 2020
まとめ
科学者はC.elegansの細胞外タンパク質の結合を制御するネットワークを発見した. この細胞外プロテオスタシスネットワークは 強化されると 宿主の防御力を高め 老化を遅らせて 毒素に対する耐性を高めます
科学分野:
- 分子生物学
- 細胞生物学
- 免疫学
背景:
- 分泌されるプロテオームは細胞間通信,先天的免疫,およびメタゾアにおける細胞外マトリックス形成に不可欠である.
- 細胞外環境は細胞内空間と比較してタンパク質に厳しい条件を課し,限られたATPの可用性がタンパク質の品質管理を妨げています.
- タンパク質の集積を防ぐ細胞外チャペロンとプロテアゼは限られている.
研究 の 目的:
- 細胞外プロテオスタシスネットワークを 系統的に分析する
- 細胞外タンパク質の結合を 制御する物質を特定する
- 病原体に反応する細胞外プロテオスタシスの役割とその宿主防御と老化への影響を調査する.
主な方法:
- 大規模なRNA干渉スクリーンで,C.elegansの分泌タンパク質をコードする遺伝子を標的とする.
- 病原性の攻撃を模倣して 毛穴形成毒素を用いて 細胞外プロテオスタシスの反応を評価する
- 関連するシグナル伝達経路の調査,特にストレスで活性化されたMAPキナーゼシグナル伝達.
主要な成果:
- 細胞外タンパク質の結合を調節する57のレギュレータを発見し,そのうちのいくつかは先天的な免疫に関連している.
- C. elegansは細胞外プロテオスタシス成分を調節し,孔を形成する毒素に反応してタンパク質の蓄積を減少させます.
- 細胞外プロテオスタシスの活性化は,ストレスによるMAPキナーゼシグナル伝達に依存する.
- 細胞外プロテオスタシス成分の過剰発現は老化を遅らせ,中毒に対する耐性を授与する.
結論:
- 細胞外プロテオスタシスは病原性刺激に反応する活性ネットワークです.
- 増強された細胞外プロテオスタシスは,分泌されたプロテオームの整合性を維持し,プロテオ毒性を防止することによって,全身的な宿主防御に寄与する.
- このネットワークは 宿主の防御,老化,毒素への抵抗に 役割を果たします
関連する概念動画
The Proteasome
1.4K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.4K
The Proteasome
9.9K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
9.9K
Amyloid Fibrils
11.4K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.4K
Molecular Chaperones and Protein Folding
19.3K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
19.3K
Regulated Protein Degradation
8.5K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.5K
Regulated Protein Degradation
2.9K
2.9K


