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肠道 F -box 蛋白调控秀丽隐杆线虫对病原菌铜绿假单胞菌的快速回避行为。

Intestinal F-box protein regulates quick avoidance behavior of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa.

机构信息

Molecular Neurobiology Research Group and DAILAB, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.

Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.

出版信息

Genes Cells. 2019 Mar;24(3):192-201. doi: 10.1111/gtc.12666. Epub 2019 Jan 28.

Abstract

In most animals, avoiding pathogenic bacteria is crucial for better health and a long life span. For this purpose, animals should be able to quickly sense the presence or uptake of pathogens. The intestine could be a candidate organ to induce escape behaviors; however, the intestinal signaling mechanism for acute regulation of neuronal activity is not well understood. Here, we show that adult Caenorhabditis elegans can respond to the pathogenic bacterium Pseudomonas aeruginosa within 30 min of exposure. This behavior was much faster than previously observed avoidance behaviors in response to P. aeruginosa. By genetic screening, we isolated a mutant defective in this quick avoidance behavior and found that the novel F-box protein FBXC-58 is involved. FBXC-58 is expressed in several tissues, but defective avoidance was rescued by expression of the protein in the intestine. Interestingly, we also found that some but not all mutants in the p38-MAPK and insulin-like signaling pathways, which function in the immune response to pathogens in the intestine, were defective in the quick avoidance behavior to P. aeruginosa. These results suggest that a novel signaling pathway in the intestine exists to regulate neuronal activity for a quick behavioral response.

摘要

在大多数动物中,避免病原体对于更好的健康和更长的寿命至关重要。为此,动物应该能够快速感知病原体的存在或摄取。肠道可能是诱导逃避行为的候选器官;然而,急性调节神经元活动的肠道信号机制尚不清楚。在这里,我们表明成年秀丽隐杆线虫在暴露于铜绿假单胞菌 30 分钟内即可对其作出反应。这种行为比以前观察到的对铜绿假单胞菌的逃避行为要快得多。通过遗传筛选,我们分离出一个在这种快速回避行为中缺陷的突变体,并发现新型 F-box 蛋白 FBXC-58 参与其中。FBXC-58 在几种组织中表达,但在肠道中表达该蛋白可挽救其回避缺陷。有趣的是,我们还发现,在肠道中对病原体的免疫反应中起作用的 p38-MAPK 和胰岛素样信号通路的一些但不是所有突变体在快速回避铜绿假单胞菌的行为中都有缺陷。这些结果表明,肠道中存在一种新的信号通路来调节神经元活动以作出快速的行为反应。

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