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.

Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex / J. Stanic, M. Carta, I. Eberini, S. Pelucchi, E. Marcello, A.A. Genazzani, C. Racca, C. Mulle, M. Di Luca, F. Gardoni. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6(2015), pp. 10181.1-10181.16.

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

J. Stanic
Primo
;
I. Eberini;S. Pelucchi;E. Marcello;M. Di Luca;F. Gardoni
Ultimo
2015

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.
Settore BIO/14 - Farmacologia
Settore MED/44 - Medicina del Lavoro
   Synapses: from molecules to higher brain function and diseases
   SYMBAD
   EUROPEAN COMMISSION
   FP7
   238608

   Discinesia indotta dalla L-DOPA nella malattia di Parkinson: nuovi meccanismi e targets molecolari.
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2010AHHP5H_002

   Shaping and reshaping the synapses: from physiology to Intellectual Disability syndromes
   FONDAZIONE CARIPLO
   2013-0795
2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/350127
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