GABAA receptor-associated phosphoinositide 3-kinase is required for insulin-induced recruitment of postsynaptic GABAA receptors
Copyright policy )GABAA receptor-associated phosphoinositide 3-kinase is required for insulin-induced recruitment of postsynaptic GABAA receptors
Type A gamma-aminobutyric acid (GABAA) receptors mediate most of the fast inhibitory synaptic transmission within the vertebrate brain. The regulation of this inhibition is vital in modulating neural activity. One regulator of GABAA receptor function is insulin, which can serve to enhance GABAA receptor-mediated miniature inhibitory postsynaptic currents, via an increase in the number of receptors at the plasma membrane. We set out to investigate the molecular mechanisms involved in the insulin-induced potentiation of GABAA receptor-mediated responses, by examining the role of phosphoinositide 3-kinase (PI3-K), a key mediator of the insulin response within the brain. We found that PI3-K associates with the GABAA receptor, and this interaction is increased following insulin treatment. Additionally, the beta2 subunit of the GABAA receptor appears to mediate the insulin-stimulated association with the N-terminal SH2 domain of the p85 subunit of PI3-K. Our results imply a mechanism whereby insulin can regulate changes in synaptic transmission through its downstream actions on the GABAA receptor.
- University of British Columbia Canada
- ETH Zurich Switzerland
- University of Fribourg Switzerland
- Institute of Biochemistry Switzerland
- Hospital for Sick Children Canada
Male, Models, Molecular, Neurons, Analysis of Variance, Patch-Clamp Techniques, In Vitro Techniques, Embryo, Mammalian, Hippocampus, Rats, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Protein Subunits, Gene Expression Regulation, Inhibitory Postsynaptic Potentials, Animals, Immunoprecipitation, Insulin, Drug Interactions, Enzyme Inhibitors, Cells, Cultured
Male, Models, Molecular, Neurons, Analysis of Variance, Patch-Clamp Techniques, In Vitro Techniques, Embryo, Mammalian, Hippocampus, Rats, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Protein Subunits, Gene Expression Regulation, Inhibitory Postsynaptic Potentials, Animals, Immunoprecipitation, Insulin, Drug Interactions, Enzyme Inhibitors, Cells, Cultured
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