Unknown

Dataset Information

0

GABA(A) receptor membrane trafficking regulates spine maturity.


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.

SUBMITTER: Jacob TC 

PROVIDER: S-EPMC2718332 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

GABA(A) receptor membrane trafficking regulates spine maturity.

Jacob Tija C TC   Wan Qin Q   Vithlani Mansi M   Saliba Richard S RS   Succol Francesca F   Pangalos Menelas N MN   Moss Stephen J SJ  

Proceedings of the National Academy of Sciences of the United States of America 20090714 30


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 siz  ...[more]

Similar Datasets

| S-EPMC2350232 | biostudies-literature
| S-EPMC6295415 | biostudies-literature
| S-EPMC4352336 | biostudies-literature
| S-EPMC6880470 | biostudies-literature
| S-EPMC2780743 | biostudies-literature
| S-EPMC7863719 | biostudies-literature
| S-EPMC3542797 | biostudies-literature
| S-EPMC5702044 | biostudies-literature
| S-EPMC5240477 | biostudies-literature
| S-EPMC3039666 | biostudies-literature