Gephyrin regulates GABAergic and glutamatergic synaptic transmission in hippocampal cell cultures.
J Biol Chem
; 286(23): 20942-51, 2011 Jun 10.
Article
in En
| MEDLINE
| ID: mdl-21507951
ABSTRACT
Gephyrin is a scaffold protein essential for stabilizing glycine and GABA(A) receptors at inhibitory synapses. Here, recombinant intrabodies against gephyrin (scFv-gephyrin) were used to assess whether this protein exerts a transynaptic action on GABA and glutamate release. Pair recordings from interconnected hippocampal cells in culture revealed a reduced probability of GABA release in scFv-gephyrin-transfected neurons compared with controls. This effect was associated with a significant decrease in VGAT, the vesicular GABA transporter, and in neuroligin 2 (NLG2), a protein that, interacting with neurexins, ensures the cross-talk between the post- and presynaptic sites. Interestingly, hampering gephyrin function also produced a significant reduction in VGLUT, the vesicular glutamate transporter, an effect accompanied by a significant decrease in frequency of miniature excitatory postsynaptic currents. Overexpressing NLG2 in gephyrin-deprived neurons rescued GABAergic but not glutamatergic innervation, suggesting that the observed changes in the latter were not due to a homeostatic compensatory mechanism. Pulldown experiments demonstrated that gephyrin interacts not only with NLG2 but also with NLG1, the isoform enriched at excitatory synapses. These results suggest a key role of gephyrin in regulating transynaptic signaling at both inhibitory and excitatory synapses.
Full text:
1
Database:
MEDLINE
Main subject:
Carrier Proteins
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Presynaptic Terminals
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Synaptic Transmission
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Hippocampus
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Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Type:
Article
Affiliation country:
Italy