Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA.
J Biol Chem. 2022 Mar;298(3):101614. doi: 10.1016/j.jbc.2022.101614. Epub 2022 Jan 29.
Microbial infections have been linked to the onset and severity of neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, but the underlying mechanisms remain largely unknown. Here, we used a genetic screen for genes involved in protection from infection-associated neurodegeneration and identified the gene mtm-10. We then validated the role of the encoded myotubularin-related protein, MTM-10, in protecting the dendrites of Caenorhabditis elegans from degeneration mediated by oxidative stress or Pseudomonas aeruginosa infection. Further experiments indicated that mtm-10 is expressed in the AWC neurons of C. elegans, where it functions in a cell-autonomous manner to protect the dendrite degeneration caused by pathogen infection. We also confirm that the changes observed in the dendrites of the animals were not because of premature death or overall sickness. Finally, our studies indicated that mtm-10 functions in AWC neurons to preserve chemosensation after pathogen infection. These results reveal an essential role for myotubularin-related protein 10 in the protection of dendrite morphology and function against the deleterious effects of oxidative stress or infection.
微生物感染与神经退行性疾病（如肌萎缩性侧索硬化症、多发性硬化症、阿尔茨海默病）的发病和严重程度有关，但潜在机制在很大程度上尚不清楚。在这里，我们使用了一种针对与感染相关的神经退行性疾病保护相关基因的遗传筛选方法，鉴定出了 mtm-10 基因。然后，我们验证了编码肌微管相关蛋白 MTM-10 在保护秀丽隐杆线虫的树突免受氧化应激或铜绿假单胞菌感染介导的变性中的作用。进一步的实验表明，mtm-10 在秀丽隐杆线虫的 AWC 神经元中表达，在细胞自主方式中发挥作用，以保护由病原体感染引起的树突变性。我们还证实，动物树突中观察到的变化不是由于过早死亡或整体疾病引起的。最后，我们的研究表明，mtm-10 在 AWC 神经元中发挥作用，以维持病原体感染后的化学感觉。这些结果揭示了肌微管相关蛋白 10 在保护树突形态和功能免受氧化应激或感染的有害影响方面的重要作用。
