A dense glycocalyx, composed of the megaDalton-sized membrane mucin MUC17, coats the microvilli in the apical brush border of transporting intestinal epithelial cells, called enterocytes. The formation of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The glycocalyx extends 1 µm into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind the positioning of MUC17 to the brush border is not known. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27 regulate apical targeting of MUC17 in enterocytes. We demonstrate that MUC17 turnover at the brush border is slow and controlled by MYO1B and SNX27. Furthermore, we report that MYO1B regulates MUC17 protein levels in enterocytes, whereas MYO5B specifically governs MUC17 levels at the brush border. Together, our results extend our understanding of the apical targeting of membrane mucins and provide mechanistic insights into how defective positioning of MUC17 render enterocytes sensitive to bacterial challenges.

中文翻译：

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MYO1B 和 MYO5B 运动蛋白以及分选连接蛋白 SNX27 调节肠皮细胞中膜粘蛋白 MUC17 的顶端靶向。


由兆道尔顿大小的膜粘蛋白 MUC17 组成的致密糖萼覆盖在运输肠上皮细胞（称为肠上皮细胞）的顶端刷状缘的微绒毛上。小鼠小肠中基于 MUC17 的糖萼的形成发生在关键的哺乳-断奶过渡期。糖萼延伸到肠腔 1 μm，防止肠道细菌直接附着在肠上皮细胞上。迄今为止，MUC17 定位到刷状边缘的机制尚不清楚。在这里，我们表明基于肌动蛋白的运动蛋白 MYO1B 和 MYO5B 以及分选连接蛋白 SNX27 调节肠皮细胞中 MUC17 的顶端靶向。我们证明刷状边界的 MUC17 周转很慢，并且受 MYO1B 和 SNX27 控制。此外，我们报道 MYO1B 调节肠皮细胞中的 MUC17 蛋白水平，而 MYO5B 特异性控制刷状边界的 MUC17 水平。总之，我们的结果扩展了我们对膜粘蛋白顶端靶向的理解，并为 MUC17 的缺陷定位如何使肠上皮细胞对细菌挑战敏感提供了机制见解。