GABAA receptor trafficking-mediated plasticity of inhibitory synapses.

GABAA receptor trafficking-mediated plasticity of inhibitory synapses.
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DOI:
10.1016/j.neuron.2011.03.024
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发表时间:
2011-05-12
期刊:
影响因子:
16.2
通讯作者:
Kilpatrick CL
Kilpatrick CL
中科院分区:
医学1区
文献类型:
--
作者:
Luscher B;Fuchs T;Kilpatrick CL

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适当的发育,神经细胞类型特异性和活动依赖性的gaba能传递调节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GABAA受体的数量直接控制GABAA能突触传递的有效性。因此,GABAA受体的调控运输对于理解健康和疾病的大脑功能至关重要。本文总结了GABAA受体在细胞表面表达、突触后积累和功能的动态适应机制方面的最新进展。这包括亚基基因表达的活性依赖性和细胞类型特异性变化,亚基组装成受体,以及胞吐、内吞循环、扩散动力学和GABAA受体的降解。我们特别关注受体相互作用蛋白、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,我们回顾了神经肽信号通路通过GABAAR运输的变化影响神经兴奋性。
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 GABAA receptors in the postsynaptic membrane directly controls the efficacy of GABAergic synaptic transmission. Thus, regulated trafficking of GABAA receptors is essential for understanding of brain function in both health and disease. Here we summarize recent progress in understanding of mechanisms that allow dynamic adaptation of cell surface expression and postsynaptic accumulation and function of GABAA 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 GABAA 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 GABAAR trafficking.
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