The intestinal intermediate filament network responds to and protects against microbial insults and toxins
The intestinal intermediate filament network responds to and protects against microbial insults and toxins
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DOI：
10.1242/dev.169482
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发表时间：
2019-01-15
期刊：
影响因子：
4.6
通讯作者：
Leube, Rudolf E.
中科院分区：
文献类型：
--
作者：
Geisler, Florian;Coch, Richard A.;Leube, Rudolf E.
肠细胞顶端细胞质中中间丝的富集在进化上是保守的，形成了一个鞘，该鞘锚定在顶端连接处并位于微绒毛刷状缘下方，这表明了保护性细胞内屏障功能。为了测试这一点，我们使用了秀丽隐杆线虫，其肠细胞被赋予了一个特别致密的中间层，称为内管。我们发现在感染杀线虫剂B后，内管结构和中间丝表达发生改变。苏云金杆菌或用其主要成孔毒素晶体蛋白Cry5B处理。由于中间丝及其调节剂的确定的基因突变导致的内管损伤导致Cry5B敏感性增加，如幼虫停滞增加、幼虫发育时间延长和存活减少所证明的。表型严重程度反映了内管改变的程度，并与毒素清除后的救援减少相关。结果提供了在体内的证据，一个适当配置的中间丝网络作为肠细胞的细胞内屏障的主要保护作用。这一概念进一步支持增加的敏感性的内管突变体的氧化和渗透胁迫。
The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionarily conserved, forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border, which suggests a protective intracellular barrier function. To test this, we used Caenorhabditis elegans, the intestinal cells of which are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We found alterations in endotube structure and intermediate filament expression upon infection with nematicidal B. thuringiensis or treatment with its major pore-forming toxin crystal protein Cry5B. Endotube impairment due to defined genetic mutations of intermediate filaments and their regulators results in increased Cry5B sensitivity as evidenced by elevated larval arrest, prolonged time of larval development and reduced survival. Phenotype severity reflects the extent of endotube alterations and correlates with reduced rescue upon toxin removal. The results provide in vivo evidence for a major protective role of a properly configured intermediate filament network as an intracellular barrier in intestinal cells. This notion is further supported by increased sensitivity of endotube mutants to oxidative and osmotic stress.