Quiescin/sulfhydryl oxidase (QSOX1) is a secreted flavoprotein that modulates cellular proliferation, migration and adhesion, roles attributed to its ability to organize the extracellular matrix. We previously showed that exogenously added QSOX1b induces smooth muscle cells migration in a process that depends on its enzymatic activity and that is mediated by hydrogen peroxide derived from Nox1, a catalytic subunit of NAD(P)H oxidases. Here, we report that exogenous QSOX1b also stimulates the migration of L929 fibroblasts and that this effect is regulated by its endocytosis. The use of endocytosis inhibitors and caveolin 1-knockdown demonstrated that this endocytic pathway is caveola-mediated. QSOX1b colocalized with Nox1 in intracellular vesicles, as detected by confocal fluorescence, suggesting that extracellular QSOX1b is endocytosed with the transmembrane Nox1. These results reveal that endosomal QSOX1b is a novel intracellular redox regulator of cell migration.

静止蛋白/巯基氧化酶 (QSOX1) 是一种分泌性黄素蛋白，可调节细胞增殖、迁移和粘附，其作用归因于其组织细胞外基质的能力。我们之前表明，外源添加的 QSOX1b 会诱导平滑肌细胞迁移，该过程取决于其酶活性，并由 NAD (P)H 氧化酶催化亚基 Nox1 衍生的过氧化氢介导。在这里，我们报道外源性 QSOX1b 也刺激 L929 成纤维细胞的迁移，并且这种效应受到其内吞作用的调节。内吞作用抑制剂和小窝蛋白 1 敲低的使用表明，这种内吞途径是小窝介导的。通过共聚焦荧光检测，QSOX1b 与 Nox1 共定位于细胞内囊泡中，表明细胞外 QSOX1b 与跨膜 Nox1 一起被内吞。这些结果表明，内体 QSOX1b 是细胞迁移的新型细胞内氧化还原调节剂。