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Science 300 (5626): 1751-1755

Copyright © 2003 by the American Association for the Advancement of Science

Requirement of AMPA Receptor GluR2 Phosphorylation for Cerebellar Long-Term Depression

Hee Jung Chung,1,2* Jordan P. Steinberg,1,2* Richard L. Huganir,1,2 David J. Linden2{dagger}

Abstract: Cerebellar long-term depression (LTD) is a model of synaptic memory that requires protein kinase C (PKC) activation and is expressed as a reduction in the number of postsynaptic {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice lacking the AMPA receptor GluR2 subunit and could be rescued by transient transfection with the wild-type GluR2 subunit. Transfection with a point mutant that eliminated PKC phosphorylation of Ser880 in the carboxy-terminal PDZ ligand of GluR2 failed to restore LTD. In contrast, transfection with a point mutant that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser880 is a critical event in the induction of cerebellar LTD.

1 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
2 Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dlinden{at}jhmi.edu

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