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.
|Titolo:||Pin1-dependent signaling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction|
|Autori:||Antonelli, R.; Pizzarelli, R.; Pedroni, A.; Fritschy, J.-M.; Del Sal, G.; Cherubini, E.; Zacchi, P.|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||10.1038/ncomms6066|
|Fulltext via DOI:||10.1038/ncomms6066|
|Appare nelle tipologie:||1.1 Journal article|