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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Antonelli R,Pizzarelli R,Pedroni A,Fritschy JM,Del Sal G,Cherubini E,Zacchi P

doi

10.1038/ncomms6066

subject

Has Abstract

pub_date

2014-10-09 00:00:00

pages

5066

issn

2041-1723

pii

ncomms6066

journal_volume

5

pub_type

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