The Residence Time of GABAARs at Inhibitory Synapses Is Determined by Direct Binding of the Receptor α1 Subunit to Gephyrin

• DOI: 10.1523/jneurosci.2001-11.2011
• Publication Date: 2011-10-12T17:02:13Z
• Authors: Jayanta Mukherjee; Karla Kretschmannova; Geraldine Gouzer; Hans-Michael Maric; Sarah Ramsden; Verena Tretter; Kirsten Harvey; Paul A. Davies; Antoine Triller; Hermann Schindelin; Stephen J. Moss
• Keywords: Gephyrin

The majority of fast synaptic inhibition in the brain is mediated by benzodiazepine-sensitive α1-subunit-containing GABA type A receptors (GABA Rs); however, our knowledge mechanisms neurons use to regulate their accumulation rudimentary. Using immunoprecipitation, we demonstrate that Rs and gephyrin are intimately associated at inhibitory synapses cultured rat neurons. In vitro reveal E-domain directly binds α1 subunit with an affinity ∼20 μ m , residues 360–375 within intracellular domain this receptor subunit. Mutating decreases both α1-containing gephyrin-positive hippocampal amplitude mIPSCs. We also for modulated Thr375, a putative phosphorylation site. Mutation Thr375 phosphomimetic, negatively charged amino acid gephyrin, therefore synapses, Finally, single-particle tracking reveals reduces diffusion specifically thereby increasing confinement these structures. Our results suggest direct binding its modulation likely be important determinants stabilization sites, modulating strength inhibition.