Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction
Copyright policy )Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction
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.
Cell Adhesion Molecules, Neuronal, 10050 Institute of Pharmacology and Toxicology, 610 Medicine & health, 1600 General Chemistry, Nerve Tissue Proteins, Hippocampus, Synaptic Transmission, Article, Physics and Astronomy (all), Mice, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, GABAergic Neurons, Phosphorylation, gamma-Aminobutyric Acid, Mice, Knockout, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Membrane Proteins, Post-Synaptic Density, Peptidylprolyl Isomerase, Receptors, GABA-A, 3100 General Physics and Astronomy, NIMA-Interacting Peptidylprolyl Isomerase, Biochemistry, Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all), Synapses, 570 Life sciences; biology, Carrier Proteins, Signal Transduction
Cell Adhesion Molecules, Neuronal, 10050 Institute of Pharmacology and Toxicology, 610 Medicine & health, 1600 General Chemistry, Nerve Tissue Proteins, Hippocampus, Synaptic Transmission, Article, Physics and Astronomy (all), Mice, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, GABAergic Neurons, Phosphorylation, gamma-Aminobutyric Acid, Mice, Knockout, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Membrane Proteins, Post-Synaptic Density, Peptidylprolyl Isomerase, Receptors, GABA-A, 3100 General Physics and Astronomy, NIMA-Interacting Peptidylprolyl Isomerase, Biochemistry, Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all), Synapses, 570 Life sciences; biology, Carrier Proteins, Signal Transduction
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