Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons.
AMPA-type glutamate receptors (AMPA-Rs) mediate a majority of excitatory synaptic transmission in the brain. In hippocampus, most AMPA-Rs are hetero-oligomers composed of GluR1/GluR2 or GluR2/GluR3 subunits. Here we show that these AMPA-R forms display different synaptic delivery mechanisms. GluR1/GluR2 receptors are added to synapses during plasticity; this requires interactions between GluR1 and group I PDZ domain proteins. In contrast, GluR2/GluR3 receptors replace existing synaptic receptors continuously; this occurs only at synapses that already have AMPA-Rs and requires interactions by GluR2 with NSF and group II PDZ domain proteins. The combination of regulated addition and continuous replacement of synaptic receptors can stabilize long-term changes in synaptic efficacy and may serve as a general model for how surface receptor number is established and maintained.
Shi
S
S
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Hayashi
Y
Y
Esteban
J A
JA
Malinow
R
R
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D052066:N-Ethylmaleimide-Sensitive Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C104723:glutamate receptor ionotropic, AMPA 3; C498737:Nsf protein, rat; C104722:glutamate receptor ionotropic, AMPA 2