Related Experiment Video
Updated: Mar 22, 2026
10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
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Neuronal ARHGAP8 controls synapse structure and AMPA receptor-mediated synaptic transmission.
Jeannette Schmidt1,2,3,4, Ângela S Inácio1,2,3, Joana Ferreira1,2,3,4
1CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Communications Biology
|March 21, 2026
Summary
This study identifies ARHGAP8 as a novel gene linked to neurodevelopmental and psychiatric disorders. Elevated ARHGAP8 levels impair synapse structure and function, suggesting its role in disease pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Aberrant neuronal synapse formation and function are key features of neurodevelopmental disorders (NDDs) and psychiatric disorders (NPDs).
- Numerous genes encoding synaptic proteins have been implicated as susceptibility factors for NDDs/NPDs.
Purpose of the Study:
- To characterize the novel susceptibility gene ARHGAP8, which encodes a Rho GTPase activating protein (RhoGAP), in the brain.
- To investigate the role of ARHGAP8 in excitatory synapses and its potential link to NDDs/NPDs.
Main Methods:
- Brain-focused characterization of ARHGAP8.
- Investigated ARHGAP8's synaptic localization in relation to the NMDA receptor subunit GluN2B.
- Manipulated ARHGAP8 levels in hippocampal neurons to assess effects on dendritic complexity, spine volume, and synaptic transmission.
Main Results:
- ARHGAP8 was identified as a novel player at excitatory synapses, with its localization associated with GluN2B.
- Increased ARHGAP8 levels reduced dendritic complexity and spine volume in hippocampal neurons.
- Elevated ARHGAP8 significantly decreased synaptic AMPA receptor-mediated transmission.
Conclusions:
- ARHGAP8 influences the morphology and function of excitatory synapses.
- ARHGAP8 is suggested as a candidate gene for further investigation in NDDs and NPDs.
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