Glutamate receptors mediate the majority of rapid excitatory synaptic transmission in the central nervous system (CNS) and play important roles 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 have found that the N- ethylmaleimide-sensitive factor (NSF), a protein involved in membrane fusion events, specifically interacts with the C terminus of the GluR2 and GluR4c subunits of AMPA receptors in vitro and in vivo. Moreover, intracellular perfusion of neurons with a synthetic peptide that competes with the interaction of NSF and AMPA receptor subunits rapidly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), suggesting that NSF regulates AMPA receptor function.
Bibliographical noteFunding Information:
S. K. was supported by a Wellcome Trust Traveling Research Fellowship. R. L. H. was supported by a grant from the National Institutes of Health (NS36715) and the Howard Hughes Medical Institute. We thank Dr. Reinhard Jahn for generously supplying mouse ascites and rabbit antiserum against NSF; Dr. Steve Traynelis for kindly supplying the minianalysis program; and Doreen Bury, Catherine Zhang, Carol Doherty, and Dr. Kimihiko Kameyama for invaluable help and constructive criticism.