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Science 287 (5461): 2262-2267

Copyright © 2000 by the American Association for the Advancement of Science

Driving AMPA Receptors into Synapses by LTP and CaMKII: Requirement for GluR1 and PDZ Domain Interaction

Yasunori Hayashi, * Song-Hai Shi, * José A. Esteban, Antonella Piccini, Jean-Christophe Poncer, dagger Roberto Malinow ddagger

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.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
*   These authors contributed equally to this work.

dagger    Present address: INSERM U261, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.

ddagger    To whom correspondence should be addressed. E-mail: malinow{at}cshl.org

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