NSF BINDING TO GLUR2 REGULATES SYNAPTIC TRANSMISSION

Here, we show that N-ethylmaleimide-sensitive fusion protein (NSF) int eracts directly and selectively with the intracellular C-terminal doma in of the GluR2 subunit of AMPA receptors. The interaction requires al l three domains of, NSF but occurs between residues Lys-844 and Gln-85 3 of rat GluR2, with Asn-851 playing a critical role. Loading of decap eptides corresponding to the NSF-binding domain of GluR2 into rat hipp ocampal CA1 pyramidal neurons results in a marked, progressive decreme nt of AMPA receptor-mediated synaptic transmission. This reduction in synaptic transmission was also observed when an anti-NSF monoclonal an tibody (mAb) was loaded into CA1 neurons. These results demonstrate a previously unsuspected direct interaction in the postsynaptic neuron b etween two major proteins involved in synaptic transmission and sugges t a rapid NSF-dependent modulation of AMPA receptor function.