AI Article Synopsis
- Guanine nucleotide exchange factors (GEFs) like Asef1 are crucial for various cell functions, particularly in the brain, but the specific role of Asef1 in neurons is not well understood.
- Asef1 was found to inhibit the proper localization of the synaptic protein PSD-95, which is important for excitatory synapses, leading to impaired synaptic transmission in hippocampal neurons.
- Neuronal activity triggers the release of Asef1 from its partner Staufen through a PI3K-dependent process, highlighting its role as a negative regulator in synaptic functions.
Article Abstract
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.
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| http://dx.doi.org/10.1111/jnc.14570 | DOI Listing |
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