Berndt Carsten, Poschmann Gereon, Stühler Kai, Holmgren Arne, Bräutigam Lars
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ; Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Life Science Center, Merowinger Platz 1, Düsseldorf, Germany.
Molecular Proteomics Laboratory, Heinrich-Heine-University, BMFZ, Düsseldorf, Germany.
Redox Biol. 2014 May 2;2:673-8. doi: 10.1016/j.redox.2014.04.012. eCollection 2014.
Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family of proteins modulating the intracellular thiol pool. Thereby, glutaredoxin 2 is important for specific redox signaling and regulates embryonic development of brain and vasculature via reversible oxidative posttranslational thiol modifications. Here, we describe that glutaredoxin 2 is also required for successful heart formation. Knock-down of glutaredoxin 2 in zebrafish embryos inhibits the invasion of cardiac neural crest cells into the primary heart field. This leads to impaired heart looping and subsequent obstructed blood flow. Glutaredoxin 2 specificity of the observed phenotype was confirmed by rescue experiments. Active site variants of glutaredoxin 2 revealed that the (de)-glutathionylation activity is required for proper heart formation. Our data suggest that actin might be one target during glutaredoxin 2 regulated cardiac neural crest cell migration and embryonic heart development. In summary, this work represents further evidence for the general importance of redox signaling in embryonic development and highlights additionally the importance of glutaredoxin 2 during embryogenesis.
谷氧还蛋白2是硫氧还蛋白家族中的一种脊椎动物特异性氧化还原酶，可调节细胞内硫醇池。因此，谷氧还蛋白2对特定的氧化还原信号传导很重要，并通过可逆的氧化翻译后硫醇修饰来调节大脑和血管的胚胎发育。在此，我们描述了谷氧还蛋白2对心脏的成功形成也是必需的。在斑马鱼胚胎中敲低谷氧还蛋白2会抑制心脏神经嵴细胞侵入初级心脏场。这会导致心脏环化受损以及随后的血流受阻。通过拯救实验证实了所观察到的表型中谷氧还蛋白2的特异性。谷氧还蛋白2的活性位点变体表明，（去）谷胱甘肽化活性是心脏正常形成所必需的。我们的数据表明，肌动蛋白可能是谷氧还蛋白2调节心脏神经嵴细胞迁移和胚胎心脏发育过程中的一个靶点。总之，这项工作进一步证明了氧化还原信号在胚胎发育中的普遍重要性，并额外强调了谷氧还蛋白2在胚胎发生过程中的重要性。
