S-nitrosylation of N-ethylmaleimide sensitive factor mediates surface expression of AMPA receptors.
Postsynaptic AMPA receptor (AMPAR) trafficking mediates some forms of synaptic plasticity that are modulated by NMDA receptor (NMDAR) activation and N-ethylmaleimide sensitive factor (NSF). We report that NSF is physiologically S-nitrosylated by endogenous, neuronally derived nitric oxide (NO). S-nitrosylation of NSF augments its binding to the AMPAR GluR2 subunit. Surface insertion of GluR2 in response to activation of synaptic NMDARs requires endogenous NO, acting selectively upon the binding of NSF to GluR2. Thus, AMPAR recycling elicited by NMDA neurotransmission is mediated by a cascade involving NMDA activation of neuronal NO synthase to form NO, leading to S-nitrosylation of NSF which is thereby activated, enabling it to bind to GluR2 and promote the receptor's surface expression.
Huang
Yunfei
Y
Department of Neuroscience, Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Man
Heng-Ye
HY
Sekine-Aizawa
Yoko
Y
Han
Yefei
Y
Juluri
Krishna
K
Luo
Hongbo
H
Cheah
Jaime
J
Lowenstein
Charles
C
Huganir
Richard L
RL
Snyder
Solomon H
SH
D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum; D003545:Cysteine / Q000378:metabolism; D003952:Diagnostic Imaging; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis / Q000502:physiology; D052066:N-Ethylmaleimide-Sensitive Proteins; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000172:deficiency; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency; D052248:Nitric Oxide Synthase Type I; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D033921:Vesicular Transport Proteins / Q000378:metabolism
D000447:Aldehydes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C110881:S-nitro-N-acetylpenicillamine; D013439:Sulfhydryl Reagents; D033921:Vesicular Transport Proteins; D000266:Adenylyl Imidodiphosphate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse; C498737:Nsf protein, rat; D010396:Penicillamine; D003545:Cysteine; C007871:glycinaldehyde; D005033:Ethylmaleimide; C104722:glutamate receptor ionotropic, AMPA 2; D019331:NG-Nitroarginine Methyl Ester