PMID:24894704

Citation	Petrini, EM, Ravasenga, T, Hausrat, TJ, Iurilli, G, Olcese, U, Racine, V, Sibarita, JB, Jacob, TC, Moss, SJ, Benfenati, F, Medini, P, Kneussel, M and Barberis, A (2014) Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. Nat Commun 5:3921
Abstract	Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABA(A)Rs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance the clustering of postsynaptic GABA(A)Rs during iLTP remain obscure. Here we demonstrate that during chemically induced iLTP (chem-iLTP), GABA(A)Rs are immobilized and confined at synapses, as revealed by single-particle tracking of individual GABA(A)Rs in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment of the scaffold protein gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent phosphorylation of GABA(A)R-β3-Ser(383). Impairment of gephyrin assembly prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization of GABA(A)Rs at synapses. Importantly, an increase of gephyrin and GABA(A)R similar to those observed during chem-iLTP in cultures were found in the rat visual cortex following an experience-dependent plasticity protocol that potentiates inhibitory transmission in vivo. Thus, phospho-GABA(A)R-β3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.
Links	PubMed PMC4059940 Online version:10.1038/ncomms4921
Keywords	Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism; Carrier Proteins/metabolism; Cells, Cultured; Hippocampus/cytology; Long-Term Potentiation/physiology; Membrane Proteins/metabolism; Mice; Neural Inhibition/physiology; Neurons/metabolism; Phosphorylation; Rats; Receptors, GABA-A/metabolism; Receptors, N-Methyl-D-Aspartate; Visual Cortex/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:KCC2A	involved_in	GO:0098970: postsynaptic neurotransmitter receptor diffusion trapping	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(GO:0060077) occurs_in:(CL:0002608) transports_or_maintains_localization_of:(GO:1902711)	Seeded From UniProt	complete

References

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