Gephyrin-independent GABA(A)R mobility and clustering during plasticity.

PloS One
Fumihiro NiwaKatsuhiko Mikoshiba

Abstract

The activity-dependent modulation of GABA-A receptor (GABA(A)R) clustering at synapses controls inhibitory synaptic transmission. Several lines of evidence suggest that gephyrin, an inhibitory synaptic scaffold protein, is a critical factor in the regulation of GABA(A)R clustering during inhibitory synaptic plasticity induced by neuronal excitation. In this study, we tested this hypothesis by studying relative gephyrin dynamics and GABA(A)R declustering during excitatory activity. Surprisingly, we found that gephyrin dispersal is not essential for GABA(A)R declustering during excitatory activity. In cultured hippocampal neurons, quantitative immunocytochemistry showed that the dispersal of synaptic GABA(A)Rs accompanied with neuronal excitation evoked by 4-aminopyridine (4AP) or N-methyl-D-aspartic acid (NMDA) precedes that of gephyrin. Single-particle tracking of quantum dot labeled-GABA(A)Rs revealed that excitation-induced enhancement of GABA(A)R lateral mobility also occurred before the shrinkage of gephyrin clusters. Physical inhibition of GABA(A)R lateral diffusion on the cell surface and inhibition of a Ca(2+) dependent phosphatase, calcineurin, completely eliminated the 4AP-induced decrease in gephyrin cluster size, but...Continue Reading

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Citations

Dec 4, 2014·Molecular and Cellular Neurosciences·Géraldine GouzerAntoine Triller
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Mar 19, 2014·The European Journal of Neuroscience·Jean-Marc Fritschy, Patrizia Panzanelli
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Feb 11, 2014·Current Protocols in Neuroscience·Misa ArizonoKatsuhiko Mikoshiba
Apr 25, 2020·Development, Growth & Differentiation·Hiroko BannaiKatsuhiko Mikoshiba
Apr 12, 2016·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Fumihiro NiwaKatsuhiko Mikoshiba
Jul 19, 2016·Journal of Neurochemistry·Miranda MeleCarlos B Duarte
Sep 8, 2018·Frontiers in Cellular Neuroscience·Joshua M Lorenz-GuertinTija C Jacob
Jun 7, 2020·Journal of Molecular Neuroscience : MN·Yogesh Kumar Dhuriya, Divakar Sharma
Jan 11, 2020·Frontiers in Molecular Neuroscience·Stephanie A Maynard, Antoine Triller
May 14, 2019·Frontiers in Cellular Neuroscience·Joshua M Lorenz-GuertinTija C Jacob

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