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Updated: Aug 18, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha
David Stellwagen1, Eric C Beattie, Jae Y Seo
1Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford Medical School, Palo Alto, California 94305, USA.
Abstract:
The proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) causes a rapid exocytosis of AMPA receptors in hippocampal pyramidal cells and is constitutively required for the maintenance of normal surface expression of AMPA receptors. Here we demonstrate that TNFalpha acts on neuronal TNFR1 receptors to preferentially exocytose glutamate receptor 2-lacking AMPA receptors through a phosphatidylinositol 3 kinase-dependent process. This increases excitatory synaptic strength while changing the molecular stoichiometry of synaptic AMPA receptors. Conversely, TNFalpha causes an endocytosis of GABA(A) receptors, resulting in fewer surface GABA(A) receptors and a decrease in inhibitory synaptic strength. These results suggest that TNFalpha can regulate neuronal circuit homeostasis in a manner that may exacerbate excitotoxic damage resulting from neuronal insults.
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