Adenomatous polyposis coli-stimulated GEF 1 (Asef1) is a negative regulator of excitatory synaptic function

J Neurochem. 2018 Dec;147(5):595-608. doi: 10.1111/jnc.14570. Epub 2018 Nov 20.


Guanine nucleotide exchange factors (GEFs) play important roles in many cellular processes, including regulation of the structural plasticity of dendritic spines. A GEF protein, adenomatous polyposis coli-stimulated GEF 1 (Asef1, ARHGEF4) is highly expressed in the nervous system. However, the function of Asef1 has not been investigated in neurons. Here, we present evidence showing that Asef1 negatively regulates the synaptic localization of postsynaptic density protein 95 (PSD-95) in the excitatory synapse by inhibiting Staufen-mediated synaptic localization of PSD-95. Accordingly, Asef1 expression impairs synaptic transmission in hippocampal cultured neurons. In addition, neuronal activity facilitates the dissociation of Asef1 from Staufen in a phosphoinositide 3 kinase (PI3K)-dependent manner. Taken together, our data reveal Asef1 functions as a negative regulator of synaptic localization of PSD-95 and synaptic transmission.

Keywords: Asef1; PSD-95; Staufen; dendritic plasticity; synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology*
  • Animals
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Disks Large Homolog 4 Protein / biosynthesis
  • Disks Large Homolog 4 Protein / genetics
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / physiology*
  • Excitatory Postsynaptic Potentials / physiology*
  • Hippocampus / cytology
  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology
  • Rats
  • Synapses / physiology*
  • Synaptic Transmission / physiology


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Endosomal Sorting Complexes Required for Transport
  • Phosphoproteins
  • RNA-Binding Proteins
  • Stau1 protein, rat
  • Adenosine Triphosphatases
  • Hgs protein, rat