相关实验视频

Updated: Jul 3, 2025

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics

Published on: June 23, 2022

Lyssavirus M 蛋白质通过重编程线粒体新陈代谢来降解神经元中的微管

Yueming Yuan^1,2, An Fang^1,2, Haoran Wang^1,2

¹State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.

|February 13, 2024

概括

狂犬病病毒 (RABV) 感染通过降解α-tubulin来破坏神经元功能. 这发生在RABVV时.

科学领域:

神经病毒学神经病毒学
细胞生物学细胞生物学
疾病的分子机制.

背景情况:

神经型病毒,包括狂犬病病毒 (RABV),可以导致神经元退化和行为变化.
通过RABV诱导神经元细胞骨蛋白质降解的精确机制仍然不完全理解.
Lyssavirus M 蛋白在破坏神经元完整性方面的作用是研究的一个关键领域.

研究的目的:

阐明RABV M蛋白诱导神经元退化的分子机制.
确定负责破坏神经元代谢和细胞骨完整性的特定病毒蛋白元素.
调查信号传递和卡尔巴因激活在RABV诱导的神经退行症中的作用.

主要方法:

神经元细胞系感染RABV并过度表达其M蛋白.
评估线粒体代谢,NAD+生产和细胞内水平.
分析来自不同lyssavirus菌株的M蛋白序列,并生成具有特定突变的重组RABV.

主要成果:

RABV感染和M蛋白过度表达通过结合Slc25a4,减少NAD+和增加细胞质Ca2+来破坏线粒体代谢.
激活的calpains降解α-tubulin,导致轴突退化.
在M蛋白中,氨基酸57对M诱导的微管降解至关重要;在这个位点的突变会减少退化.

结论:

Lyssavirus M 蛋白触发了一连串涉及线粒体功能障碍,释放和calpain 激活的过程,导致神经退行.
M蛋白的第57个氨基酸是其神经毒性潜力的关键决定因素.
准这种特定的病毒蛋白相互作用为治疗狂犬病病毒诱导的神经损伤提供了潜在的治疗干预途径.

关键词:

lyssavirus lyssavirus 是一种类型的病毒.线粒体的新陈代谢神经元退行症神经元退行症

更多相关视频

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

Published on: August 4, 2022

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

相关概念视频

Lysosomal Hydrolases

Lysosomal Hydrolases

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,...

ATP Synthase: Mechanism

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...

Intracellular Movement of Viruses and Bacteria

Intracellular Movement of Viruses and Bacteria

Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...