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

Author

Listed:
  • Roberta Antonelli

    (International School for Advanced Studies (SISSA))

  • Rocco Pizzarelli

    (International School for Advanced Studies (SISSA))

  • Andrea Pedroni

    (International School for Advanced Studies (SISSA))

  • Jean-Marc Fritschy

    (Institute of Pharmacology and Toxicology, University of Zurich)

  • Giannino Del Sal

    (Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie (LNCIB)
    Universita' degli Studi di Trieste)

  • Enrico Cherubini

    (International School for Advanced Studies (SISSA)
    European Brain Research Institute (EBRI))

  • Paola Zacchi

    (International School for Advanced Studies (SISSA))

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.

Suggested Citation

  • Roberta Antonelli & Rocco Pizzarelli & Andrea Pedroni & Jean-Marc Fritschy & Giannino Del Sal & Enrico Cherubini & Paola Zacchi, 2014. "Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6066
    DOI: 10.1038/ncomms6066
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