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Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism

Lookup NU author(s): Dr John Williams, Dr Elek Molnar


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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 α-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.

Publication metadata

Author(s): Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL, Henley JM

Publication type: Article

Publication status: Published

Journal: Neuron

Year: 1999

Volume: 23

Issue: 2

Pages: 365-376

Print publication date: 01/06/1999

ISSN (print): 0896-6273

ISSN (electronic): 1097-4199

Publisher: Cell Press


DOI: 10.1016/S0896-6273(00)80786-2

PubMed id: 10399941


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Funder referenceFunder name
Wellcome Trust
GTH12528Biotechnology and Biological Sciences Research Council