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The Journal of Neuroscience, May 15, 1999, 19(10):3926-3934

Postsynaptic Density-93 Interacts with the 2 Glutamate Receptor Subunit at Parallel Fiber Synapses

Katherine W. Roche¹, C. Dune Ly¹, Ronald S. Petralia¹, Ya-Xian Wang¹, Aaron W. McGee², David S. Bredt², and Robert J. Wenthold¹

¹ Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, and ² Department of Physiology and Programs in Biomedical Sciences and Neuroscience, University of California at San Francisco School of Medicine, San Francisco, California 94143-0444

The glutamate receptor subunit 2 has a unique distribution at the parallel fiber-Purkinje cell synapse of the cerebellum, which is developmentally regulated such that 2 occurs at both parallel fiber synapses and climbing fiber synapses early in development but is restricted to parallel fiber synapses in adult animals. To identify proteins that might be involved in the trafficking or docking of 2 receptors, we screened a yeast two-hybrid library with the cytosolic C terminus of 2 and isolated a member of the postsynaptic density (PSD)-95 family of proteins, which are known to interact with the extreme C termini of NMDA receptors. We find that 2 binds specifically to PSD-93, which is enriched in Purkinje cells. In addition, PSD-93 clusters 2 when they are coexpressed in heterologous cells, and clustering is disrupted by point mutations of 2 that disrupt the 2-PSD-93 interaction. Ultrastructural localization of PSD-93 and 2 shows they are colocalized at parallel fiber synapses; however, PSD-93 also is present at climbing fiber synapses of the adult rat, where 2 is not found, indicating that the presence of PSD-93 alone is not sufficient for determining the synaptic expression of 2.

Key words: glutamate receptor; receptor targeting; yeast two-hybrid; synaptic anchor; cerebellum; synaptic receptor regulation

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19103926-09$05.00/0

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