Qin Wan

Publications (2)19.36 Total impact

• Article: GABA(A) receptor membrane trafficking regulates spine maturity.

  Tija C Jacob, Qin Wan, Mansi Vithlani, Richard S Saliba, Francesca Succol, Menelas N Pangalos, Stephen J Moss
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  ABSTRACT: GABA(A) receptors (GABA(A)Rs), 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 beta3 subunits (beta3S408/9A), which have reduced binding to the clathrin adaptor protein-2, a critical regulator of GABA(A)R endocytosis. Neurons expressing beta3S408/9A subunits exhibited increases in the number and size of inhibitory synapses, together with enhanced inhibitory synaptic transmission due to reduced GABA(A)R endocytosis. Furthermore, neurons expressing beta3S408/9A 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 GABA(A)Rs. Therefore, regulating the efficacy of synaptic inhibition by modulating GABA(A)R membrane trafficking may play a critical role in regulating spine maturity with significant implications for synaptic plasticity together with behavior.
  Proceedings of the National Academy of Sciences 08/2009; 106(30):12500-5. · 9.68 Impact Factor
• Source

  Available from: pnas.org

  Article: GABAA receptor membrane trafficking regulates spine maturity

  Tija C. Jacob, Qin Wan, Mansi Vithlani, Richard S. Saliba, Francesca Succol, Menelas N. Pangalos, Stephen J. Moss
  [show abstract] [hide abstract]
  ABSTRACT: 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.
  Proceedings of the National Academy of Sciences 07/2009; 106(30):12500-12505. · 9.68 Impact Factor