Activity of Arhgef4 is modulated through Staufen1 in neurons.

Kina Lee, Ki-Seo Yoo, Young-Seok Park, Hyong Kyu Kim

Neuroscience letters 2021 Jun 21

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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. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Kina Lee, Ki-Seo Yoo, Young-Seok Park, Hyong Kyu Kim. Activity of Arhgef4 is modulated through Staufen1 in neurons. Neuroscience letters. 2021 Jun 21;756:135962