Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction.
To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.
Hayashi
Y
Y
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Shi
S H
SH
Esteban
J A
JA
Piccini
A
A
Poncer
J C
JC
Malinow
R
R
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation; D008564:Membrane Potentials; D009154:Mutation; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D011506:Proteins; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins