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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}

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Activity Level-Dependent Synapse-Specific AMPA Receptor Trafficking Regulates Transmission Kinetics.
J. J. Zhu (2009)
J. Neurosci. 29, 6320-6335
   Abstract »    Full Text »    PDF »
{beta}-Amyloid Impairs AMPA Receptor Trafficking and Function by Reducing Ca2+/Calmodulin-dependent Protein Kinase II Synaptic Distribution.
Z. Gu, W. Liu, and Z. Yan (2009)
J. Biol. Chem. 284, 10639-10649
   Abstract »    Full Text »    PDF »
The function of glutamatergic synapses is not perturbed by severe knockdown of 4.1N and 4.1G expression.
C. Wozny, J. Breustedt, F. Wolk, F. Varoqueaux, S. Boretius, A. R. Zivkovic, A. Neeb, J. Frahm, D. Schmitz, N. Brose, et al. (2009)
J. Cell Sci. 122, 735-744
   Abstract »    Full Text »    PDF »
Synaptopodin Regulates Plasticity of Dendritic Spines in Hippocampal Neurons.
A. Vlachos, E. Korkotian, E. Schonfeld, E. Copanaki, T. Deller, and M. Segal (2009)
J. Neurosci. 29, 1017-1033
   Abstract »    Full Text »    PDF »
Sequential Changes in AMPA Receptor Targeting in the Developing Neocortical Excitatory Circuit.
J. Brill and J. R. Huguenard (2008)
J. Neurosci. 28, 13918-13928
   Abstract »    Full Text »    PDF »
AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region.
T. Abrahamsson, B. Gustafsson, and E. Hanse (2008)
J Neurophysiol 100, 2605-2614
   Abstract »    Full Text »    PDF »

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