Essrich C, Lorez M, Benson J A, Fritschy J M, Lüscher B
Institute of Pharmacology, University of Zurich, Switzerland.
Nat Neurosci. 1998 Nov;1(7):563-71. doi: 10.1038/2798.
Most fast inhibitory neurotransmission in the brain is mediated by GABAA 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 GABAA receptor subtypes. Loss of GABAA 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 GABAA 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 GABAA receptors in vivo.
大脑中大多数快速抑制性神经传递由GABAA受体介导，这些受体主要位于突触后，由多种α和β亚基以及γ2亚基组成。虽然γ2亚基对于受体组装和转运到细胞表面并非必需，但我们在此表明，它是主要突触后GABAA受体亚型聚集所必需的。γ2亚基缺陷小鼠以及这些小鼠的培养皮层神经元中GABAA受体簇的丧失，与突触聚集分子桥连蛋白和突触GABA能功能的丧失同时发生。相反，抑制桥连蛋白表达会导致GABAA受体簇的丧失。因此，γ2亚基和桥连蛋白是同一突触复合体的相互依赖成分，这对于体内丰富的GABAA受体亚型在突触后的聚集至关重要。
