Postsynaptic clustering of major GABAA receptor subtypes requires the γ2 subunit and gephyrin

Postsynaptic clustering of major GABAA receptor subtypes requires the γ2 subunit and gephyrin
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DOI:
10.1038/2798
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发表时间:
1998-11-01
影响因子:
25
通讯作者:
Lüscher, B
Lüscher, B
中科院分区:
医学1区
文献类型:
--
作者:
Essrich, C;Lorez, M;Lüscher, B

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脑中大多数快速抑制性神经传递由GABA(A)受体介导,其主要是突触后的并且由不同的α和β亚基以及γ 2亚基组成。尽管γ 2亚基对于受体组装和易位到细胞表面不是必需的,但我们在这里表明,它是主要突触后GABA(A)受体亚型聚集所必需的。在γ 2亚单位缺陷的小鼠中,以及在来自这些小鼠的培养的皮层神经元中,GABA(A)受体簇的损失由突触成簇分子桥蛋白和突触GABA能功能的损失引起。相反,抑制桥蛋白表达会导致GABA(A)受体簇的损失。因此,γ 2亚基和桥蛋白是同一突触复合体的相互依赖的组分,该复合体对于体内GABA(A)受体的丰富亚型的突触后聚集是关键的。
Most fast inhibitory neurotransmission in the brain is mediated by GABA(A) receptors, which are mainly postsynaptic and consist of diverse alpha and beta subunits together with the gamma 2 subunit. Although the gamma 2 subunit is not necessary for receptor assembly and translocation to the cell surface, we show here that it is required for clustering of major postsynaptic GABA(A) receptor subtypes. Loss of GABA(A) receptor clusters in mice deficient in the gamma 2 subunit, and in cultured cortical neurons from these mice, is paralleled by loss of the synaptic clustering molecule gephyrin and synaptic GABAergic function. Conversely, inhibiting gephyrin expression causes loss of GABA(A) receptor clusters. The gamma 2 subunit and gephyrin are thus interdependent components of the same synaptic complex that is critical for postsynaptic clustering of abundant subtypes of GABA(A) receptors in vivo.