Mechanism of stabilization of glutamate receptors at postsynaptic membranes

Mechanism of stabilization of glutamate receptors at postsynaptic membranes

NMDA receptor (NMDAR) composition and synaptic retention represent pivotal features in the physiology and pathology of excitatory synapses.

Scientists 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.

Authors 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.

http://www.nature.com/ncomms/2015/151218/ncomms10181/full/ncomms10181.html
 
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