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The Journal of Neuroscience, February 1, 2000, 20(3):1260-1271
A Developmental Change in NMDA Receptor-Associated Proteins at
Hippocampal Synapses
Nathalie
Sans1,
Ronald
S.
Petralia1,
Ya-Xian
Wang1,
Jaroslav
Blahos II1,
Johannes W.
Hell2, 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
Pharmacology, University of Wisconsin, Madison, Wisconsin
53706-1532
The membrane-associated guanylate kinases
[Chapsyn-110/postsynaptic density-93 (PSD-93), synapse-associated
protein-90 (SAP-90)/PSD-95, and SAP-102] are believed to cluster
and anchor NMDA receptors at the synapse and to play a role in signal
transduction. We have investigated the developmental changes in
expression of these proteins in rat hippocampus using biochemical
analyses and quantitative immunogold electron microscopy. At postnatal
day 2 (P2), SAP-102 was highly expressed, whereas PSD-93 and PSD-95
were low. SAP-102 expression increased during the first week, stayed
stable through P35, and showed a reduced expression at 6 months. From
P2 through 6 months, PSD-93 and PSD-95 increased. For PSD-95, the
percent of labeled synapses increased almost threefold with age,
whereas the number of gold particles per labeled synapse did not change significantly, suggesting that the increase in PSD-95 is attributable primarily to an increase in the number of synapses containing PSD-95.
In contrast, for SAP-102, both percent labeled synapses and the number
of gold particles per labeled synapse decreased during this time. From
Western blots of hippocampus and immunogold analysis of CA1 synapses,
the high expression of NR2B at P2 coincides with the high level of
SAP-102 at synapses, whereas the later expression of NR2A coincides
with that of PSD-93 and PSD-95. To determine whether the changes in
PSD-93/95 and SAP-102 reflect preferred associations with NR2A and
NR2B, respectively, we measured co-immunoprecipitation in the adult
hippocampus. These studies suggest that there is a preference for
complexes of NR2A/PSD-93/95 and NR2B/SAP-102. These results indicate
that individual receptor-associated proteins may have specific
functions that are critical to synapse development.
Key words:
MAGUKs; PSD-93; PSD-95; SAP-102; glutamate receptors; postsynaptic density; hippocampus
Copyright © 2000 Society for Neuroscience 0270-6474/00/2031260-12$05.00/0
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