与免疫相关的基因由与戈尔吉功能和ARF-1 GTPase相关的膜应激通路刺激
Matthew J Fanelli1, Christofer M Welsh1,2, Dominique S Lui1
1Program in Molecular Medicine, UMASS Chan Medical School, Worcester, MA, USA.
Science advances
|December 6, 2023
概括
在C. elegans中,免疫相关基因 (ILG) 对病原体的攻击和酸丁胆 (PC) 脂质水平的变化作出反应. 这表明ILG是影响分泌功能的膜应激反应的一部分.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 免疫相关基因 (ILG) 在C. elegans*中通过病原体的挑战被上调.
- 在脂质新陈代谢的扰乱期间,ILG也被上调,但潜在的机制尚不清楚.
- 了解免疫反应和代谢变化之间的联系对于细胞健康至关重要.
研究的目的:
- 调查病原体攻击和脂质代谢变化的机制,都会激活ILG.
- 探索酸丁胆 (PC) 水平和分泌器官在ILG激活中的作用.
- 为了确定ILG上调是否是对分泌应激的协调反应.
主要方法:
- 使用C. elegans作为一个模型生物.
- 研究ILG激活,以应对酸丁胆 (PC) 水平的变化.
- 采用RNA干扰 (RNAi) 针对ADP-核糖化因子*arf-1*来破坏戈尔吉和分泌功能.
- 评估了ILG敲击对记者蛋白和补充融合蛋白的分泌的影响.
主要成果:
- 当酸丁胆 (PC) 水平在分泌器官膜中发生变化时,ILG会被激活.
- 通过*arf-1*RNAi破坏戈尔吉和分泌功能也会激活ILG.
- 发现低PC水平限制了ARF-1功能,这表明ILG激活的机制是由脂质代谢驱动的.
- 选择ILG的RNAi导致蛋白质分泌的缺陷和对病原体反应的蛋白质的积累.
结论:
- 一些ILG的升级监管是对蜂贩运变化的协调反应.
- 这种反应可能有助于抵消分泌功能的压力,将脂质代谢与免疫基因表达联系起来.
- 这些发现表明,膜应激反应的新途径在内质网膜外运行.
相关概念视频
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
MAPK Signaling Cascades
5.6K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.6K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Rab Proteins
3.9K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.9K
Amplifying Signals via Second Messengers
7.0K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
7.0K
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K


