Department of Medicine and Microbiology, Graduate Program in Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
Department of Neurosurgery, Graduate Program in Neuroscience, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
Neurosci Lett. 2021 Jun 21;756:135962. doi: 10.1016/j.neulet.2021.135962. Epub 2021 May 19.
The role of Arhgef4, also known as adenomatous polyposis coli (APC)-stimulated guanine nucleotide exchange factor 1 (Asef1), has been identified in colorectal cancers. Interestingly, Arhgef4 is more highly expressed in brain regions than intestinal regions, suggesting a role in neurons. In our previous study, we reported that Arhgef4 negatively regulates the level of PSD-95 in excitatory post-synaptic regions by binding with Staufen1. However, modulation of Arhgef4 guanine nucleotide exchange factor (GEF) activity in neurons has not been reported. We examined the configuration of protein interactions when Arhgef4 binds to APC and/or Staufen1. Arhgef4 simultaneously binds to Staufen1 with APC. Staufen1 overexpression blocked the GEF activity of Arhgef4. Consistent with this, Staufen1 overexpression blocked the Arhgef4-induced increase in dendritic protrusions in cultured neurons. Taken together, our data suggest that the GEF activity of Arhgef4 could be negatively modulated by Staufen1 binding.
Arhgef4，也称为腺瘤性结肠息肉病（APC）刺激鸟嘌呤核苷酸交换因子 1（Asef1），其在结直肠癌中的作用已经得到确定。有趣的是，Arhgef4 在大脑区域的表达高于肠道区域，这表明其在神经元中发挥作用。在我们之前的研究中，我们报告称 Arhgef4 通过与 Staufen1 结合来负调控兴奋性突触后区域中 PSD-95 的水平。然而，神经元中 Arhgef4 鸟嘌呤核苷酸交换因子（GEF）活性的调节尚未报道。我们检查了 Arhgef4 与 APC 和/或 Staufen1 结合时的蛋白质相互作用结构。Arhgef4 与 APC 同时与 Staufen1 结合。Staufen1 的过表达阻断了 Arhgef4 的 GEF 活性。与此一致的是，Staufen1 的过表达阻断了 Arhgef4 诱导的培养神经元中树突状突起的增加。总之，我们的数据表明，Staufen1 的结合可能负调控 Arhgef4 的 GEF 活性。
