GABA type a receptor trafficking and the architecture of synaptic inhibition

Ubiquitous expression of GABA type A receptors (GABA(A)R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABA(A)Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition. The molecular mechanisms constituting receptor trafficking to and from these compartments therefore dictate the efficacy of GABA(A)R function. Here we review the current understanding of how GABA(A)Rs traffic through biogenesis, plasma membrane transport, and degradation. Emphasis is placed on discussing novel GABAergic synaptic proteins, receptor and scaffolding post-translational modifications, activity-dependent changes in GABA(A)R confinement, and neuropeptide and neurosteroid mediated changes. We further highlight modern techniques currently advancing the knowledge of GABA(A)R trafficking and clinically relevant neurodevelopmental diseases connected to GABAergic dysfunction. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 238-270, 2018