通过非激活V-ATPase的溶解体功能障碍驱动C. elegans的先天免疫反应
Xuepiao Pu1, Bin Qi1
1Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
Cell reports
|April 28, 2024
概括
由于真空ATPase (V-ATPase) 不活化引起的功能障碍溶解体,增强了天生的免疫力. 这种反应需要DVE-1和线粒体展开蛋白反应 (UPRmt),但由于能源成本而减缓了动物的生长.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 病原体通过准真空ATPase (V-ATPase) 来破坏溶解体功能,从而损害了酸化和融合.
- 检测 lysosomal 功能障碍和启动免疫反应的细胞机制在很大程度上是未知的.
研究的目的:
- 为了研究细胞是否可以检测功能失调的溶解体,并建立免疫反应.
- 阐明分子途径链接 lysosomal 功能障碍与先天免疫.
主要方法:
- 利用RNA干扰 (RNAi) 在模型生物中使V-ATPase (vha RNAi) 失活.
- 研究了V-ATPase和DVE-1之间的相互作用.
- 评估了DVE-1的核定位作为线粒体展开蛋白质反应 (UPRmt) 诱导的标记.
- 量化病原体耐药性和动物生长率.
主要成果:
- 无活化V-ATPase增强了对细菌感染的天生的免疫力.
- lysosomal V-ATPase 与 DVE-1 相互作用; V-ATPase 的非激活促进了 DVE-1 的核定位,激活了 UPRmt 和免疫基因.
- 由V-ATPase无活化诱导的病原体耐药性取决于dve-1及其下游效应因子.
- 不同的RNAi导致动物生长速度减慢,这表明免疫反应和生长之间存在能量权衡.
结论:
- 功能障碍的溶解体,特别是由于V-ATPase的失活,可以触发可检测的先天免疫反应.
- DVE-1/UPRmt通路对于调解这种溶酶体到免疫信号来说至关重要.
- 免疫激活会产生大量的能源成本,影响宿主生长,并强调了在防御过程中节能的重要性.
相关概念视频
01:22Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
01:36Delivery Pathways to the Lysosome
6.4K
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...
6.4K
01:24Caspases
12.5K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.5K
01:27Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K