RT Journal Article SR Electronic T1 Loss of Postsynaptic GABAA Receptor Clustering in Gephyrin-Deficient Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9289 OP 9297 DO 10.1523/JNEUROSCI.19-21-09289.1999 VO 19 IS 21 A1 Matthias Kneussel A1 Johann Helmut Brandstätter A1 Bodo Laube A1 Sabine Stahl A1 Ulrike Müller A1 Heinrich Betz YR 1999 UL http://www.jneurosci.org/content/19/21/9289.abstract AB The tubulin-binding protein gephyrin, which anchors the inhibitory glycine receptor (GlyR) at postsynaptic sites, decorates GABAergic postsynaptic membranes in various brain regions, and postsynaptic gephyrin clusters are absent from cortical cultures of mice deficient for the GABAA receptor γ2 subunit. Here, we investigated the postsynaptic clustering of GABAA receptors in gephyrin knock-out (geph −/−) mice. Both in brain sections and cultured hippocampal neurons derived fromgeph −/− mice, synaptic GABAA receptor clusters containing either the γ2 or the α2 subunit were absent, whereas glutamate receptor subunits were normally localized at postsynaptic sites. Western blot analysis and electrophysiological recording revealed that normal levels of functional GABAAreceptors are expressed in geph −/− neurons, however the pool size of intracellular GABAA receptors appeared increased in the mutant cells. Thus, gephyrin is required for the synaptic localization of GlyRs and GABAA receptors containing the γ2 and/or α2 subunits but not for the targeting of these receptors to the neuronal plasma membrane. In addition, gephyrin may be important for efficient membrane insertion and/or metabolic stabilization of inhibitory receptors at developing postsynaptic sites.