Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction
Roberta Antonelli1, Rocco Pizzarelli1, Andrea Pedroni1
1Department of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea 265, 34136 Trieste, Italy.
None:
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.
More Related Videos
Related Concept Videos
IP3/DAG Signaling Pathway
GPCR Desensitization
Amplifying Signals via Enzymatic Cascade
Activation and Inactivation of G Proteins
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...


