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Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction

Roberta Antonelli, Rocco Pizzarelli, Andrea Pedroni, Jean-Marc Fritschy, Giannino Del Sal, Enrico Cherubini and Paola Zacchi ()
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Roberta Antonelli: International School for Advanced Studies (SISSA)
Rocco Pizzarelli: International School for Advanced Studies (SISSA)
Andrea Pedroni: International School for Advanced Studies (SISSA)
Jean-Marc Fritschy: Institute of Pharmacology and Toxicology, University of Zurich
Giannino Del Sal: Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie (LNCIB)
Enrico Cherubini: International School for Advanced Studies (SISSA)
Paola Zacchi: International School for Advanced Studies (SISSA)

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract The cell adhesion molecule Neuroligin2 (NL2) is localized selectively at GABAergic synapses, where it interacts with the scaffolding protein gephyrin in the post-synaptic density. However, the role of this interaction for formation and plasticity of GABAergic synapses is unclear. Here, we demonstrate that endogenous NL2 undergoes proline-directed phosphorylation at its unique S714-P consensus site, leading to the recruitment of the peptidyl-prolyl cis–trans isomerase Pin1. This signalling cascade negatively regulates NL2’s ability to interact with gephyrin at GABAergic post-synaptic sites. As a consequence, enhanced accumulation of NL2, gephyrin and GABAA receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1−/−) associated with an increase in amplitude of spontaneous GABAA-mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6066

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DOI: 10.1038/ncomms6066

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