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.
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, United Kingdom.
J
J
Noel
G S
GS
Ralph
L
L
Pickard
J
J
Williams
E
E
Molnar
J B
JB
Uney
G L
GL
Collingridge
J M
JM
Henley
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