GABAA receptor membrane trafficking regulates spine maturity
2009
Jacob, Tija C. | Wan, Qin | Vithlani, Mansi | Saliba, Richard S. | Succol, Francesca | Pangalos, Menelas N. | Moss, Stephen J.
GABAA receptors (GABAARs), the principal sites of synaptic inhibition in the brain, are dynamic entities on the neuronal cell surface, but the role their membrane trafficking plays in shaping neuronal activity remains obscure. Here, we examined this by using mutant receptor β3 subunits (β3S408/9A), which have reduced binding to the clathrin adaptor protein-2, a critical regulator of GABAAR endocytosis. Neurons expressing β3S408/9A subunits exhibited increases in the number and size of inhibitory synapses, together with enhanced inhibitory synaptic transmission due to reduced GABAAR endocytosis. Furthermore, neurons expressing β3S408/9A subunits had deficits in the number of mature spines and reduced accumulation of postsynaptic density protein-95 at excitatory synapses. This deficit in spine maturity was reversed by pharmacological blockade of GABAARs. Therefore, regulating the efficacy of synaptic inhibition by modulating GABAAR membrane trafficking may play a critical role in regulating spine maturity with significant implications for synaptic plasticity together with behavior.
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