Loss of postsynaptic GABAA receptor clustering in gephyrin-deficient mice
Loss of postsynaptic GABAA receptor clustering in gephyrin-deficient mice
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DOI：
10.1523/jneurosci.19-21-09289.1999
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发表时间：
1999-11-01
影响因子：
5.3
通讯作者：
Betz, H
中科院分区：
文献类型：
--
作者：
Kneussel, M;Brandstätter, JH;Betz, H
微管蛋白结合蛋白桥蛋白将抑制性甘氨酸受体（GlyR）锚定在突触后位点，修饰不同脑区的GABA能突触后膜，GABA（A）受体γ 2亚基缺陷小鼠的皮质培养物中不存在突触后桥蛋白簇。在这里，我们研究了GABA（A）受体在geph -/-小鼠的突触后聚集。在脑切片和培养的来自geph -/-小鼠的海马神经元中，不存在含有γ 2或α 2亚基的突触GABA（A）受体簇，而谷氨酸受体亚基通常位于突触后位点。Western印迹分析和电生理记录显示，正常水平的功能性GABA（A）受体在geph -/-神经元中表达，然而，细胞内GABA（A）受体池的大小似乎在突变细胞中增加。因此，桥蛋白是含有γ 2和/或α 2亚基的GlyR和GABA（A）受体的突触定位所需的，但不是这些受体靶向神经元质膜所需的。此外，桥蛋白可能是重要的有效膜插入和/或抑制性受体在发育突触后位点的代谢稳定。
The tubulin-binding protein gephyrin, which anchors the inhibitory glycine receptor (GlyR) at postsynaptic sites, decorates GABAergic postsynaptic membranes in various brain regions, and postsynaptic gephyrin clusters are absent from cortical cultures of mice deficient for the GABA(A) receptor gamma 2 subunit. Here, we investigated the postsynaptic clustering of GABA(A) receptors in gephyrin knock-out (geph -/-) mice. Both in brain sections and cultured hippocampal neurons derived from geph -/- mice, synaptic GABA(A) receptor clusters containing either the gamma 2 or the alpha 2 subunit were absent, whereas glutamate receptor subunits were normally localized at postsynaptic sites. Western blot analysis and electrophysiological recording revealed that normal levels of functional GABA(A) receptors are expressed in geph -/- neurons, however the pool size of intracellular GABA(A) receptors appeared increased in the mutant cells. Thus, gephyrin is required for the synaptic localization of GlyRs and GABA(A) receptors containing the gamma 2 and/or alpha 2 subunits but not for the targeting of these receptors to the neuronal plasma membrane. In addition, gephyrin may be important for efficient membrane insertion and/or metabolic stabilization of inhibitory receptors at developing postsynaptic sites.