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 GABA A receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1�/�) associated with an increase in amplitude of spontaneous GABA A -mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction. � 2014 Macmillan Publishers Limited. All rights reserved.

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

Antonelli, Roberta;Pizzarelli, Rocco;Pedroni, Andrea;Cherubini, Enrico;Zacchi, Paola
2014

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 GABA A receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1�/�) associated with an increase in amplitude of spontaneous GABA A -mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction. � 2014 Macmillan Publishers Limited. All rights reserved.
5
1
14
5066
10.1038/ncomms6066
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197815/
Antonelli, Roberta; Pizzarelli, Rocco; Pedroni, Andrea; Fritschy, J. M.; Del Sal, G.; Cherubini, Enrico; Zacchi, Paola
File in questo prodotto:
File Dimensione Formato  
ncomms6066.pdf

accesso aperto

Descrizione: Open Access Journal
Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 2.65 MB
Formato Adobe PDF
2.65 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/30026
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 33
social impact