Jäverfelt Sofia, Hellsén Gustaf, Kaji Izumi, Goldenring James R, Pelaseyed Thaher
bioRxiv. 2023 Mar 7:2023.03.06.530313. doi: 10.1101/2023.03.06.530313.
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 establishment of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The enterocytic glycocalyx extends 1 µm into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind apical targeting of MUC17 to the brush border remains unknown. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27 regulate the intracellular trafficking 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 intracellular trafficking of membrane mucins and provide mechanistic insights into how defective trafficking pathways render enterocytes sensitive to bacterial invasion.
一种由百万道尔顿大小的膜黏蛋白MUC17组成的致密糖萼，覆盖在被称为肠上皮细胞的转运肠道上皮细胞顶端刷状缘的微绒毛上。基于MUC17的糖萼在小鼠小肠中的形成发生在关键的哺乳-断奶过渡期。肠上皮细胞糖萼向肠腔延伸1微米，可防止肠道细菌直接附着在肠上皮细胞上。迄今为止，MUC17顶端靶向至刷状缘背后的机制仍不清楚。在此，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调节肠上皮细胞中MUC17的细胞内运输。我们证明刷状缘处MUC17的周转缓慢且受MYO1B和SNX27控制。此外，我们报告MYO1B调节肠上皮细胞中MUC17的蛋白质水平，而MYO5B则特异性地控制刷状缘处MUC17的水平。总之，我们的结果扩展了我们对膜黏蛋白细胞内运输的理解，并为有缺陷的运输途径如何使肠上皮细胞对细菌入侵敏感提供了机制性见解。
