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Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex

Author

Listed:
  • Jennifer Stanic

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

  • Mario Carta

    (Institut Interdisciplinaire de Neurosciences, University of Bordeaux)

  • Ivano Eberini

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

  • Silvia Pelucchi

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

  • Elena Marcello

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

  • Armando A. Genazzani

    (Università degli Studi del Piemonte Orientale ‘Amedeo Avogadro’)

  • Claudia Racca

    (Institute of Neuroscience, Newcastle University)

  • Christophe Mulle

    (Institut Interdisciplinaire de Neurosciences, University of Bordeaux)

  • Monica Di Luca

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

  • Fabrizio Gardoni

    (DiSFeB, Università degli Studi di Milano, Via Balzaretti 9)

Abstract

NMDA receptor (NMDAR) composition and synaptic retention represent pivotal features in the physiology and pathology of excitatory synapses. Here, we identify Rabphilin 3A (Rph3A) as a new GluN2A subunit-binding partner. Rph3A is known as a synaptic vesicle-associated protein involved in the regulation of exo- and endocytosis processes at presynaptic sites. We find that Rph3A is enriched at dendritic spines. Protein–protein interaction assays reveals that Rph3A N-terminal domain interacts with GluN2A(1349–1389) as well as with PSD-95(PDZ3) domains, creating a ternary complex. Rph3A silencing in neurons reduces the surface localization of synaptic GluN2A and NMDAR currents. Moreover, perturbing GluN2A/Rph3A interaction with interfering peptides in organotypic slices or in vivo induces a decrease of the amplitude of NMDAR-mediated currents and GluN2A density at dendritic spines. In conclusion, Rph3A interacts with GluN2A and PSD-95 forming a complex that regulates NMDARs stabilization at postsynaptic membranes.

Suggested Citation

  • Jennifer Stanic & Mario Carta & Ivano Eberini & Silvia Pelucchi & Elena Marcello & Armando A. Genazzani & Claudia Racca & Christophe Mulle & Monica Di Luca & Fabrizio Gardoni, 2015. "Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex," Nature Communications, Nature, vol. 6(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10181
    DOI: 10.1038/ncomms10181
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