RGD Reference Report - Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. - Rat Genome Database

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Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP.

Authors: Petrini, Enrica Maria  Ravasenga, Tiziana  Hausrat, Torben J  Iurilli, Giuliano  Olcese, Umberto  Racine, Victor  Sibarita, Jean-Baptiste  Jacob, Tija C  Moss, Stephen J  Benfenati, Fabio  Medini, Paolo  Kneussel, Matthias  Barberis, Andrea 
Citation: Petrini EM, etal., Nat Commun. 2014 Jun 4;5:3921. doi: 10.1038/ncomms4921.
RGD ID: 12050118
Pubmed: PMID:24894704   (View Abstract at PubMed)
PMCID: PMC4059940   (View Article at PubMed Central)
DOI: DOI:10.1038/ncomms4921   (Journal Full-text)

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-ß3-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-ß3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.



Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Camk2a  (calcium/calmodulin-dependent protein kinase II alpha)


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