Jäverfelt Sofia, Hellsén Gustaf, Kaji Izumi, Goldenring James R, Pelaseyed Thaher
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden.
Epithelial Biology Center, Vanderbilt University Medical Center; Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A.
Biochem J. 2025 Jan 8;482(1):1-23. doi: 10.1042/BCJ20240204.
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 renders enterocytes sensitive to bacterial challenges.
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。小鼠小肠中基于MUC17的糖萼形成于关键的哺乳-断奶过渡期。糖萼向肠腔延伸1微米，可防止肠道细菌直接附着于肠上皮细胞。迄今为止，MUC17定位于刷状缘背后的机制尚不清楚。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可调节肠上皮细胞中MUC17的顶端靶向定位。我们证明，刷状缘处MUC17的周转缓慢，受MYO1B和SNX27调控。此外，我们报告称，MYO1B调节肠上皮细胞中MUC17的蛋白水平，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顶端靶向定位的理解，并为MUC17定位缺陷如何使肠上皮细胞对细菌攻击敏感提供了机制性见解。
