NSF binding to GluR2 regulates synaptic transmission

Neuron. 1998 Jul;21(1):87-97. doi: 10.1016/s0896-6273(00)80517-6.

Abstract

Here, we show that N-ethylmaleimide-sensitive fusion protein (NSF) interacts directly and selectively with the intracellular C-terminal domain of the GluR2 subunit of AMPA receptors. The interaction requires all three domains of NSF but occurs between residues Lys-844 and Gln-853 of rat GluR2, with Asn-851 playing a critical role. Loading of decapeptides corresponding to the NSF-binding domain of GluR2 into rat hippocampal CA1 pyramidal neurons results in a marked, progressive decrement of AMPA receptor-mediated synaptic transmission. This reduction in synaptic transmission was also observed when an anti-NSF monoclonal antibody (mAb) was loaded into CA1 neurons. These results demonstrate a previously unsuspected direct interaction in the postsynaptic neuron between two major proteins involved in synaptic transmission and suggest a rapid NSF-dependent modulation of AMPA receptor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Molecular Sequence Data
  • N-Ethylmaleimide-Sensitive Proteins
  • Neurons / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / physiology
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism*
  • Synaptic Transmission / physiology*
  • Vesicular Transport Proteins*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Excitatory Amino Acid Agonists
  • Receptors, AMPA
  • Receptors, Glutamate
  • Vesicular Transport Proteins
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, rat