Institute of Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, 07743, Jena, Germany.
Centre of Electron Microscopy, Jena University Hospital - Friedrich Schiller University Jena, 07743, Jena, Germany.
Sci Rep. 2020 Jul 7;10(1):11156. doi: 10.1038/s41598-020-66111-9.
Brush borders of intestinal epithelial cells are mandatory for nutrient uptake. Yet, which actin nucleators are crucial for forming the F-actin bundles supporting microvilli and the actin filaments of the terminal web, in which microvilli are rooted, is unknown. We show that mice lacking the actin nucleator Cobl surprisingly did not display reduced microvilli densities or changes in microvillar F-actin bundles or microvilli diameter but particularly in the duodenum displayed increased microvillar length. Interestingly, Cobl-deficient mice furthermore showed a significant widening of the terminal web. Quantitative analyses of high-resolution cryo-scanning electron microscopy (EM) of deep-etched duodenum samples revealed that Cobl is specifically important for the formation of fine filaments in the central terminal web that connect the apical structure of the terminal web underlying the plasma membrane, the microvilli rootlets and the basal structure of the terminal web with each other. Thus, the actin nucleator Cobl is critically involved in generating one of the cellular structures of the brush border-decorated apical cortex of enterocytes representing the absorptive intestinal surface.
肠道上皮细胞的刷状缘对于营养物质的摄取是必需的。然而，对于形成支持微绒毛的 F-肌动蛋白束和微绒毛根部的终末网的肌动蛋白丝，哪些肌动蛋白成核因子是至关重要的，目前还不清楚。我们发现，缺乏肌动蛋白成核因子 Cobl 的小鼠并没有表现出微绒毛密度降低或微绒毛 F-肌动蛋白束或微绒毛直径的变化，但在十二指肠中，微绒毛的长度却特别增加。有趣的是，Cobl 缺陷小鼠的终末网还明显变宽。对深度蚀刻的十二指肠样本进行高分辨率冷冻扫描电子显微镜（EM）的定量分析表明，Cobl 对于形成中央终末网中的细纤维特别重要，这些纤维将位于质膜下的终末网的顶端结构、微绒毛根和终末网的基底结构彼此连接起来。因此，肌动蛋白成核因子 Cobl 对于生成刷状缘装饰的肠上皮细胞顶端皮质的细胞结构之一，即吸收性肠表面，是至关重要的。
