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Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice.

Kneussel, M. and Brandstätter, J. H. and Laube, Bodo and Stahl, S. and Müller, U. and Betz, H. (1999):
Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice.
In: The Journal of neuroscience : the official journal of the Society for Neuroscience, pp. 9289-97, 19, (21), ISSN 1529-2401, [Article]

Abstract

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 GABA(A) receptor gamma2 subunit. Here, we investigated the postsynaptic clustering of GABA(A) receptors in gephyrin knock-out (geph -/-) mice. Both in brain sections and cultured hippocampal neurons derived from geph -/- mice, synaptic GABA(A) receptor clusters containing either the gamma2 or the alpha2 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 GABA(A) receptors are expressed in geph -/- neurons, however the pool size of intracellular GABA(A) receptors appeared increased in the mutant cells. Thus, gephyrin is required for the synaptic localization of GlyRs and GABA(A) receptors containing the gamma2 and/or alpha2 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.

Item Type: Article
Erschienen: 1999
Creators: Kneussel, M. and Brandstätter, J. H. and Laube, Bodo and Stahl, S. and Müller, U. and Betz, H.
Title: Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice.
Language: English
Abstract:

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 GABA(A) receptor gamma2 subunit. Here, we investigated the postsynaptic clustering of GABA(A) receptors in gephyrin knock-out (geph -/-) mice. Both in brain sections and cultured hippocampal neurons derived from geph -/- mice, synaptic GABA(A) receptor clusters containing either the gamma2 or the alpha2 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 GABA(A) receptors are expressed in geph -/- neurons, however the pool size of intracellular GABA(A) receptors appeared increased in the mutant cells. Thus, gephyrin is required for the synaptic localization of GlyRs and GABA(A) receptors containing the gamma2 and/or alpha2 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.

Journal or Publication Title: The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume: 19
Number: 21
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
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Date Deposited: 12 Apr 2011 09:14
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