GSTP proteins are metabolic enzymes involved in the removal of oxidative stress and intracellular signaling and also have inhibitory effects on JNK activity. However, the functions of Gstp proteins in the developing brain are unknown. In mice, there are three Gstp proteins, Gstp1, 2 and 3, whereas there is only one GSTP in humans. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, we found that Gstp1 was expressed beginning at E15.5 in the cortex, but Gstp2 and 3 started expressing at E18.5. Gstp 1 and 2 knockdown (KD) caused decreased neurite number in cortical neurons, implicating them in neurite initiation. Using in utero electroporation (IUE) to knock down Gstp1 and 2 in layer 2/3 pyramidal neurons in vivo, we found abnormal swelling of the apical dendrite at P3 and reduced neurite number at P15. Using time-lapse live imaging, we found that the apical dendrite orientation was skewed compared with the control. We explored the molecular mechanism and found that JNK inhibition rescued reduced neurite number caused by Gstp knockdown, indicating that Gstp regulates neurite formation through JNK signaling. Thus, we found novel functions of Gstp proteins in neurite initiation during cortical development. These findings not only provide novel functions of Gstp proteins in neuritogenesis during cortical development but also help us to understand the complexity of neurite formation.

中文翻译：

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谷胱甘肽 S-转移酶 Pi (Gstp) 蛋白调节发育中的大脑皮层的神经突发生


GSTP 蛋白是参与消除氧化应激和细胞内信号传导的代谢酶，并且对 JNK 活性也具有抑制作用。然而，Gstp 蛋白在发育中的大脑中的功能尚不清楚。小鼠中存在三种 Gstp 蛋白：Gstp1、2 和 3，而人类中只有一种 GSTP。通过逆转录聚合酶链反应（RT-PCR）分析，我们发现Gstp1在皮质中从E15.5开始表达，而Gstp2和3在E18.5开始表达。 Gstp 1 和 2 敲除 (KD) 导致皮质神经元中的神经突数量减少，这表明它们参与了神经突的形成。使用子宫内电穿孔 (IUE) 敲低体内 2/3 层锥体神经元中的 Gstp1 和 2，我们发现 P3 处的顶端树突异常肿胀，P15 处的神经突数量减少。使用延时实时成像，我们发现顶端树突方向与对照相比是倾斜的。我们探索了分子机制，发现 JNK 抑制可挽救 Gstp 敲低引起的神经突数量减少，表明 Gstp 通过 JNK 信号传导调节神经突形成。因此，我们发现 Gstp 蛋白在皮质发育过程中神经突起始中的新功能。这些发现不仅提供了 Gstp 蛋白在皮质发育过程中神经突发生中的新功能，而且有助于我们了解神经突形成的复杂性。