NSF binding to GluR2 regulates synaptic transmission.
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.
Department of Biological Sciences, Faculty of Medicine, Kyoto University, Japan.
A
A
Nishimune
J T
JT
Isaac
E
E
Molnar
J
J
Noel
S R
SR
Nash
M
M
Tagaya
G L
GL
Collingridge
S
S
Nakanishi
J M
JM
Henley
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D033921:Vesicular Transport Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D033921:Vesicular Transport Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat