バクテリア の ガス 皮 は 細胞 死 の 古代 の 仕組み を 明らかに し て い ます
Alex G Johnson1,2, Tanita Wein3, Megan L Mayer4
1Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|January 13, 2022
まとめ
ヒトの細胞死と免疫に不可欠なガズダーミンタンパク質には 細菌の対称性があります これらのバクテリアのガスダーミンは 毛穴を形成し 制御された細胞死の 古代の起源を示しています
科学分野:
- 細胞生物学
- 微生物学
- 免疫学
背景:
- ヒトのガスダーミンタンパク質は膜の毛穴を形成し,サイトカインを放出し,細胞死 (ピロプトーシス) を誘発する.
- このプロセスは 病原体に対する免疫防御と 癌抑制に不可欠です
- インフラマソームシグナル伝達とカスパース媒介の分裂がヒトガスダーミンの活性化を誘発する.
研究 の 目的:
- バクテリアにおけるガスダーミンの同類体の存在と機能を調査する.
- バクテリアのガス皮膚活性化と毛穴形成の構造的およびメカニズム的基礎を解明する.
- 細胞死亡経路の 進化的起源を理解するために
主な方法:
- バクテリアのゲノムにおけるガスダーミンの同類体の生物情報識別
- 細菌のガスダーミン構造を決定するための構造生物学技術 (例えば,X線結晶学).
- プロテアゼによるバクテリアのガスダーミンの活性化と毛穴形成を研究する生化学分析
主要な成果:
- 菌根菌と細菌の細胞死に対する防御に関与する細菌のガスダーミンホモログの発見
- 構造分析により,不活性な細菌のガスダーミンの脂質変異によって安定した孔形成ドメインが確認された.
- バクテリアのガスダーミンは,特定のカスパーゼのようなプロテアゼによって活性化され,抑制ペプチドの分裂と除去が伴う.
- 細胞が活性化すると 毛穴が集まり 膜が壊れ 細胞が死滅します
結論:
- ピロプトーシスは 制御された細胞死の一種で 細菌と動物が共有する 古代のメカニズムです
- 細菌のガスダーミンは,ガスダーミンが媒介する孔形成の基本原理を理解するためのモデルを提供します.
- この発見は 細胞死亡経路と その進化史の理解を 広げています
関連する概念動画
01:30Overview of Cell Death
7.9K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.9K
01:16Necrosis
5.0K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
5.0K
01:17The Extrinsic Apoptotic Pathway
6.7K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.7K
01:18Autophagic Cell Death
3.6K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.6K
01:31The Intrinsic Apoptotic Pathway
7.0K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.0K
01:30Apoptosis
12.1K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
12.1K