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GABAA receptor trafficking and its role in the dynamic modulation of neuronal inhibition

2008; Nature Portfolio; Volume: 9; Issue: 5 Linguagem: Inglês

10.1038/nrn2370

1471-0048

Tija C. Jacob, Stephen J. Moss, Rachel Jurd,

Ion channel regulation and function

GABAA receptors mediate most inhibitory synaptic transmission, and their assembly and trafficking in neurons is tightly regulated. Moss and colleagues review our current knowledge about the molecular mechanisms that regulate GABAAreceptor trafficking and their contribution to neuronal function. GABA (γ-aminobutyric acid) type A receptors (GABAARs) mediate most fast synaptic inhibition in the mammalian brain, controlling activity at both the network and the cellular levels. The diverse functions of GABA in the CNS are matched not just by the heterogeneity of GABAARs, but also by the complex trafficking mechanisms and protein–protein interactions that generate and maintain an appropriate receptor cell-surface localization. In this Review, we discuss recent progress in our understanding of the dynamic regulation of GABAAR composition, trafficking to and from the neuronal surface, and lateral movement of receptors between synaptic and extrasynaptic locations. Finally, we highlight a number of neurological disorders, including epilepsy and schizophrenia, in which alterations in GABAAR trafficking occur.