细胞死亡中NINJ1介导的血破裂的结构基础
Morris Degen1, José Carlos Santos2, Kristyna Pluhackova3
1Biozentrum, University of Basel, Basel, Switzerland.
Nature
|May 17, 2023
概括
在编程细胞死亡过程中,蛋白质ninjurin-1 (NINJ1) 积极破裂细胞膜. NINJ1形成了细丝结构,覆盖并破坏了等离子体膜,揭示了其在临床细胞死亡中的作用.
科学领域:
- 细胞生物学
- 分子生物学
- 结构生物学
背景情况:
- 在真核生物中,编程细胞死亡通常涉及血破裂.
- 膜破裂以前归因于透压力,现在被理解为一个活跃的过程.
- 在许多细胞死亡途径中,蛋白质ninjurin-1 (NINJ1) 调解膜破裂.
研究的目的:
- 确定NINJ1的结构.
- 阐明NINJ1引起膜破裂的机制.
- 了解NINJ1在细胞死亡中的作用.
主要方法:
- 超分辨率显微镜观察死亡细胞中的NINJ1组件.
- 用冷电子显微镜来确定NINJ1丝的结构.
- 分子动力学模拟来分析线程膜相互作用.
- 用于验证NINJ1功能的位点定向突变.
主要成果:
- 在垂死的细胞膜中,NINJ1形成了多样化,大丝状的组合.
- 通过冷电磁检测, 发现NINJ1纤维是密集的跨膜α螺旋.
- 模拟显示NINJ1丝可以封闭和稳定膜边缘.
- 突变性证实了NINJ1的两螺旋在线索形成和膜破裂中的作用.
结论:
- 在临床细胞死亡过程中,NINJ1聚合成两性纤维,破裂血膜.
- NINJ1 作为细胞膜的交互组件, 作为一个断点.
- 这项研究揭示了NINJ1调节细胞死亡的结构和机制.
相关概念视频
Necrosis
4.6K
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...
4.6K
The Extrinsic Apoptotic Pathway
6.5K
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...
6.5K
The Intrinsic Apoptotic Pathway
6.7K
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...
6.7K
Overview of Cell Death
7.4K
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...
7.4K
Apoptosis
11.6K
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...
11.6K
NF-κB-dependent Signaling Pathway
7.6K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.6K


