期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：22
页码：12860-12865
DOI：10.1073/pnas.96.22.12860
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Synaptic localization of {gamma}-aminobutyric acid type A (GABAA) receptors is a prerequisite for synaptic inhibitory function, but the mechanism by which different receptor subtypes are localized to postsynaptic sites is poorly understood. The {gamma}2 subunit and the postsynaptic clustering protein gephyrin are required for synaptic localization and function of major GABAA receptor subtypes. We now show that transgenic overexpression of the {gamma}3 subunit in {gamma}2 subunit-deficient mice restores benzodiazepine binding sites, benzodiazepine-modulated whole cell currents, and postsynaptic miniature currents, suggesting the formation of functional, postsynaptic receptors. Moreover, the {gamma}3 subunit can substitute for {gamma}2 in the formation of GABAA receptors that are synaptically clustered and colocalized with gephyrin in vivo. These clusters were formed even in brain regions devoid of endogenous {gamma}3 subunit, indicating that the factors present for clustering of {gamma}2 subunit-containing receptors are sufficient to cluster {gamma}3 subunit-containing receptors. The GABAA receptor and gephyrin-clustering properties of the ectopic {gamma}3 subunit were also observed for the endogenous {gamma}3 subunit, but only in the absence of the {gamma}2 subunit, suggesting that the {gamma}3 subunit is at a competitive disadvantage with the {gamma}2 subunit for clustering of postsynaptic GABAA receptors in wild-type mice.
