Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α
D Stellwagen, EC Beattie, JY Seo… - Journal of …, 2005 - Soc Neuroscience
Journal of Neuroscience, 2005•Soc Neuroscience
The proinflammatory cytokine tumor necrosis factor-α (TNFα) 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
TNFα 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 …
AMPA receptors in hippocampal pyramidal cells and is constitutively required for the
maintenance of normal surface expression of AMPA receptors. Here we demonstrate that
TNFα 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 …
The proinflammatory cytokine tumor necrosis factor-α (TNFα) 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 TNFα 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, TNFα causes an endocytosis of GABAA receptors, resulting in fewer surface GABAA receptors and a decrease in inhibitory synaptic strength. These results suggest that TNFα can regulate neuronal circuit homeostasis in a manner that may exacerbate excitotoxic damage resulting from neuronal insults.
Soc Neuroscience