Mucus is made of enormous mucin glycoproteins that polymerize by disulfide crosslinking in the Golgi apparatus. QSOX1 is a catalyst of disulfide bond formation localized to the Golgi. Both QSOX1 and mucins are highly expressed in goblet cells of mucosal tissues, leading to the hypothesis that QSOX1 catalyzes disulfide-mediated mucin polymerization. We found that knockout mice lacking QSOX1 had impaired mucus barrier function due to production of defective mucus. However, an investigation on the molecular level revealed normal disulfide-mediated polymerization of mucins and related glycoproteins. Instead, we detected a drastic decrease in sialic acid in the gut mucus glycome of the QSOX1 knockout mice, leading to the discovery that QSOX1 forms regulatory disulfides in Golgi glycosyltransferases. Sialylation defects in the colon are known to cause colitis in humans. Here we show that QSOX1 redox control of sialylation is essential for maintaining mucosal function.

中文翻译：

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二硫化物催化剂QSOX1通过调节高尔基糖基转移酶维持结肠粘膜屏障

粘液由巨大的粘蛋白糖蛋白组成，这些糖蛋白通过高尔基体中的二硫化物交联聚合。QSOX1 是定位于高尔基体的二硫键形成催化剂。QSOX1 和粘蛋白均在粘膜组织的杯状细胞中高表达，从而导致 QSOX1 催化二硫化物介导的粘蛋白聚合的假设。我们发现缺乏 QSOX1 的敲除小鼠由于产生有缺陷的粘液而导致粘液屏障功能受损。然而，分子水平的研究揭示了正常的二硫化物介导的粘蛋白和相关糖蛋白的聚合。相反，我们检测到 QSOX1 敲除小鼠肠道粘液糖组中唾液酸的急剧减少，导致发现 QSOX1 在高尔基糖基转移酶中形成调节性二硫化物。已知结肠中的唾液酸化缺陷会导致人类结肠炎。在这里，我们表明 QSOX1 对唾液酸化的氧化还原控制对于维持粘膜功能至关重要。