Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
Neuron. 2011 May 12;70(3):385-409. doi: 10.1016/j.neuron.2011.03.024.
Proper developmental, neural cell-type-specific, and activity-dependent regulation of GABAergic transmission is essential for virtually all aspects of CNS function. The number of GABA(A) receptors in the postsynaptic membrane directly controls the efficacy of GABAergic synaptic transmission. Thus, regulated trafficking of GABA(A) receptors is essential for understanding brain function in both health and disease. Here we summarize recent progress in the understanding of mechanisms that allow dynamic adaptation of cell surface expression and postsynaptic accumulation and function of GABA(A) receptors. This includes activity-dependent and cell-type-specific changes in subunit gene expression, assembly of subunits into receptors, as well as exocytosis, endocytic recycling, diffusion dynamics, and degradation of GABA(A) receptors. In particular, we focus on the roles of receptor-interacting proteins, scaffold proteins, synaptic adhesion proteins, and enzymes that regulate the trafficking and function of receptors and associated proteins. In addition, we review neuropeptide signaling pathways that affect neural excitability through changes in GABA(A)R trafficking.
适当的发育、神经细胞类型特异性和活动依赖性调节 GABA 能传递对于中枢神经系统功能的几乎所有方面都是必不可少的。突触后膜中 GABA(A) 受体的数量直接控制 GABA 能突触传递的效率。因此，GABA(A) 受体的调节性转运对于理解健康和疾病中的大脑功能至关重要。在这里，我们总结了理解允许 GABA(A) 受体的细胞表面表达和突触后积累和功能进行动态适应的机制的最新进展。这包括亚基基因表达、亚基组装成受体以及胞吐作用、内吞循环、扩散动力学和 GABA(A) 受体降解方面的活性依赖性和细胞类型特异性变化。特别是，我们专注于受体相互作用蛋白、支架蛋白、突触粘附蛋白以及调节受体和相关蛋白的运输和功能的酶的作用。此外，我们还回顾了通过改变 GABA(A)R 转运来影响神经兴奋性的神经肽信号通路。
