Glutamate receptors mediate the majority of rapid excitatory synaptic
transmission in the central nervous system (CNS) and play important ro
les in synaptic plasticity and neuronal development. Recently, protein
-protein interactions with the C-terminal domain of glutamate receptor
subunits have been shown to be involved in the modulation of receptor
function and clustering at excitatory synapses. In this paper, we hav
e found that the N-ethylmaleimide-sensitive factor (NSF), a protein in
volved in membrane fusion events, specifically interacts with the C te
rminus of the GluR2 and GluR4c subunits of AMPA receptors in vitro and
in vivo. Moreover, intracellular perfusion of neurons with a syntheti
c peptide that competes with the interaction of NSF and AMPA receptor
subunits rapidly decreases the amplitude of miniature excitatory posts
ynaptic currents (mEPSCs), suggesting that NSF regulates AMPA receptor
function.