Association of gephyrin with synaptic and extrasynaptic GABAA receptors varies during development in cultured hippocampal neurons
Association of gephyrin with synaptic and extrasynaptic GABAA receptors varies during development in cultured hippocampal neurons
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DOI：
10.1016/s1044-7431(03)00069-1
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发表时间：
2003-06-01
影响因子：
3.5
通讯作者：
Bessis, A
中科院分区：
文献类型：
--
作者：
Danglot, L;Triller, A;Bessis, A
一些研究报道了海马神经元中 GABAA 受体的突触外簇。然而，它们的功能相关性以及突触发生过程中与 gephyrin 相关的进化仍然未知。我们分析了培养的海马神经元突触发生过程中 GABA 能突触主要蛋白的表达模式。我们发现以 VIAAT 和 GAD-65 表达为特征的 GABA 能末端在谷氨酸能末端 3 至 7 天后分化。在突触后侧，GABAAR-β3 亚基首先扩散，然后当 GABA 能末端分化且 gephyrin 形成大簇时聚集。这些蛋白质的共定位很高，并且随着发育而增加。在后期阶段，GABAAR beta3 簇与 gephyrin 在突触以及突触外位点共定位。 GABAAR γ2 亚基直接表达为簇，其首先位于突触外且与 gephyrin 无关。随后，GABAAR γ2 亚基与突触和/或突触外部位的 gephyrin 相关。我们的数据表明 GABAAR gamma2 亚基簇的形成与 gephyrin 无关。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
Several studies have reported extrasynaptic clusters of GABAA receptors in hippocampal neurons. Yet their functional relevance as well as their evolution in relation with gephyrin during synaptogenesis remain unknown. We have analyzed the expression pattern of the main proteins of the GABAergic synapses during synaptogenesis in cultured hippocampal neurons. We found that GABAergic terminals, characterized by VIAAT and GAD-65 expression, differentiated 3 to 7 days after the glutamatergic endings. At the postsynaptic side, the GABAAR-beta3 subunit was first diffuse and then clustered when GABAergic terminals differentiated and gephyrin formed large clusters. Colocalization of these proteins was high and increased with development. At later stages, GABAAR beta3 clusters colocalized with gephyrin at synaptic but also at extrasynaptic sites. GABAAR gamma2 subunits were directly expressed as clusters which were first extrasynaptic and not associated with gephyrin. Subsequently, the GABAAR gamma2 subunits associated with gephyrin at synaptic and/or extrasynaptic sites. Our data indicate that formation of GABAAR gamma2 subunit clusters is gephyrin independent. (C) 2003 Elsevier Science (USA). All rights reserved.