Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism.
Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.
Noel
J
J
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, United Kingdom.
Ralph
G S
GS
Pickard
L
L
Williams
J
J
Molnar
E
E
Uney
J B
JB
Collingridge
G L
GL
Henley
J M
JM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015151:Immunoblotting; D007150:Immunohistochemistry; D052066:N-Ethylmaleimide-Sensitive Proteins; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D033921:Vesicular Transport Proteins; C104724:glutamate receptor ionotropic, AMPA 4; C498737:Nsf protein, rat; C104722:glutamate receptor ionotropic, AMPA 2