Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261.
Dev Neurobiol. 2018 Mar;78(3):238-270. doi: 10.1002/dneu.22536. Epub 2017 Sep 19.
Ubiquitous expression of GABA type A receptors (GABA 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 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 R function. Here we review the current understanding of how GABA 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 R confinement, and neuropeptide and neurosteroid mediated changes. We further highlight modern techniques currently advancing the knowledge of GABA R trafficking and clinically relevant neurodevelopmental diseases connected to GABAergic dysfunction. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 238-270, 2018.
中枢神经系统中 GABA 型 A 受体 (GABA R) 的普遍表达确立了它们在协调神经功能和发育的大多数方面的核心作用。GABA 能神经传递的失调表现在许多人类健康障碍和疾病中，在某些情况下，针对这些受体的药物可以缓解这些障碍和疾病。位于细胞表面和 GABA 能突触后位点的 GABA Rs 的数量或活性的精确变化直接影响抑制的强度。因此，构成受体从这些隔室运输到这些隔室的分子机制决定了 GABA R 功能的功效。在这里，我们回顾了目前对 GABA Rs 如何通过生物发生、质膜运输和降解进行运输的理解。重点讨论了新型 GABA 能突触蛋白、受体和支架翻译后修饰、GABA R 限制的活性依赖性变化以及神经肽和神经甾体介导的变化。我们进一步强调了目前正在推进 GABA R 运输知识的现代技术以及与 GABA 能功能障碍相关的临床相关神经发育疾病。Wiley Periodicals, Inc. 2017 版权所有。发育神经生物学 78:238-270,2018。
