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.
|Titolo:||Rabphilin 3A retains NMDA receptors at synaptic sites through interaction with GluN2A/PSD-95 complex|
STANIC, JENNIFER (Primo)
GARDONI, FABRIZIO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/44 - Medicina del Lavoro
|Progetto:||Synapses: from molecules to higher brain function and diseases|
Discinesia indotta dalla L-DOPA nella malattia di Parkinson: nuovi meccanismi e targets molecolari.
Shaping and reshaping the synapses: from physiology to Intellectual Disability syndromes
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||10.1038/ncomms10181|
|Appare nelle tipologie:||01 - Articolo su periodico|