Quiescin sulfhydryl oxidase 1 (QSOX1) catalyzes the formation of disulfide bonds in protein substrates. Unlike other enzymes with related activities, which are commonly found in the endoplasmic reticulum, QSOX1 is localized to the Golgi apparatus or secreted. QSOX1 is upregulated in quiescent fibroblast cells and secreted into the extracellular environment, where it contributes to extracellular matrix assembly. QSOX1 is also upregulated in adenocarcinomas, though the extent to which it is secreted in this context is currently unknown. To achieve a better understanding of factors that dictate QSOX1 localization and function, we aimed to determine how post-translational modifications affect QSOX1 trafficking and activity. We found a highly conserved N-linked glycosylation site to be required for QSOX1 secretion from fibroblasts and other cell types. Notably, QSOX1 lacking a glycan at this site arrives at the Golgi, suggesting that it passes endoplasmic reticulum quality control but is not further transported to the cell surface for secretion. The QSOX1 transmembrane segment is dispensable for Golgi localization and secretion, as fully luminal and transmembrane variants displayed the same trafficking behavior. This study provides a key example of the effect of glycosylation on Golgi exit and contributes to an understanding of late secretory sorting and quality control.

中文翻译：

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槲皮素巯基氧化酶1（QSOX1）糖位点突变扰动分泌，但不影响高尔基体定位

槲皮素巯基氧化酶1（QSOX1）催化蛋白质底物中二硫键的形成。与通常在内质网中发现的具有相关活性的其他酶不同，QSOX1位于高尔基体中或被分泌出来。QSOX1在静止的成纤维细胞中被上调，并分泌到细胞外环境中，在那里它有助于细胞外基质的组装。QSOX1在腺癌中也被上调，尽管目前尚不清楚其在这种情况下的分泌程度。为了更好地了解决定QSOX1定位和功能的因素，我们旨在确定翻译后修饰如何影响QSOX1的运输和活性。我们发现从成纤维细胞和其他细胞类型分泌QSOX1所需的高度保守的N-连接的糖基化位点。值得注意的是，在该位点缺少聚糖的QSOX1到达高尔基体，表明它已通过内质网质量控制，但并未进一步转运至细胞表面进行分泌。QSOX1跨膜片段对于高尔基体的定位和分泌是必不可少的，因为完全的腔内和跨膜变体显示出相同的运输行为。这项研究提供了糖基化对高尔基体出口的影响的关键例子，并有助于后期分泌分类和质量控制的理解。因为完全管腔和跨膜变体显示出相同的运输行为。这项研究提供了糖基化对高尔基体出口的影响的关键例子，并有助于后期分泌分类和质量控制的理解。因为完全管腔和跨膜变体显示出相同的运输行为。这项研究提供了糖基化对高尔基体出口的影响的关键例子，并有助于后期分泌分类和质量控制的理解。