The γ2 subunit of GABAA receptors is required for maintenance of receptors at mature synapses
The γ2 subunit of GABAA receptors is required for maintenance of receptors at mature synapses
复制标题
DOI：
10.1016/s1044-7431(03)00202-1
复制
发表时间：
2003-10-01
影响因子：
3.5
通讯作者：
Lüscher, B
中科院分区：
文献类型：
--
作者：
Schweizer, C;Balsiger, S;Lüscher, B
GABA(A) 受体氯离子通道的 gamma2 亚基是正常通道功能和突触发生过程中这些受体的突触后聚集所必需的。此外，GABA(A) 受体功能被认为有助于神经元出生后的正常成熟。因此，γ2 缺陷神经元中突触后 GABA(A) 受体的丧失可能反映了由于通道功能降低而导致的神经元成熟缺陷。在这里，我们使用 Cre-loxP 策略来检查成熟突触处 gamma2 亚基的聚类功能。出生后第三周删除 γ2 亚基会导致苯二氮卓结合位点丧失，并同时丧失突触后 GABA(A) 受体和 gephyrin 的点状免疫反应性。因此，gamma2 亚基通过一种在成熟神经元中起作用的机制（而不仅限于未成熟神经元）促进 GABA（A） 受体和 gephyrin 的突触后定位，可能是通过与参与突触 GABA（A） 受体运输的蛋白质相互作用而实现的。 (C) 2003 Elsevier Inc. 保留所有权利。
The gamma2 subunit of GABA(A) receptor chloride channels is required for normal channel function and for postsynaptic clustering of these receptors during synaptogenesis. In addition, GABA(A) receptor function is thought to contribute to normal postnatal maturation of neurons. Loss of postsynaptic GABA(A) receptors in gamma2-deficient neurons might therefore reflect a deficit in maturation of neurons due to the reduced channel function. Here, we have used the Cre-loxP strategy to examine the clustering function of the gamma2 subunit at mature synapses. Deletion of the gamma2 subunit in the third postnatal week resulted in loss of benzodiazepine-binding sites and parallel loss of punctate immunoreactivity for postsynaptic GABA(A) receptors and gephyrin. Thus, the gamma2 subunit contributes to postsynaptic localization of GABA(A) receptors and gephyrin by a mechanism that is operant in mature neurons and not limited to immature neurons, roost likely through interaction with proteins involved in trafficking of synaptic GABA(A) receptors. (C) 2003 Elsevier Inc. All rights reserved.