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The Journal of Neuroscience, February 15, 1998, 18(4):1217-1229
Heterogeneity in the Molecular Composition of Excitatory
Postsynaptic Sites during Development of Hippocampal Neurons in
Culture
Anuradha
Rao1,
Eunjoon
Kim2,
Morgan
Sheng2 and
Ann Marie
Craig1
1 Department of Cell and Structural Biology, University
of Illinois at Urbana-Champaign, Urbana, Illinois 61801, and
2 Howard Hughes Medical Institute, Massachusetts General
Hospital, Department of Neurobiology, Harvard Medical School, Boston,
Massachusetts 02114
To determine their roles in the assembly of glutamatergic
postsynaptic sites, we studied the distributions of NMDA- and AMPA-type glutamate receptors; the NMDA receptor-interacting proteins
-actinin-2, PSD-95, and chapsyn; and the PSD-95-associated protein
GKAP during the development of hippocampal neurons in culture. NMDA
receptors first formed nonsynaptic proximal dendrite shaft clusters
within 2-5 d. AMPA receptors were diffuse at this stage and began to cluster on spines at 9-10 d. NMDA receptor clusters remained partially nonsynaptic and mainly distinct from AMPA receptor clusters until after
3 weeks in culture, when the two began to colocalize at spiny synaptic
sites. Thus, the localization of NMDA and AMPA receptors must be
regulated by different mechanisms. -Actinin-2 colocalized with the
NMDA receptor only at spiny synaptic clusters, but not at shaft
nonsynaptic or synaptic clusters, suggesting a modulatory role in the
anchoring of NMDA receptor at spines. PSD-95, chapsyn, and GKAP were
present at some, but not all, nonsynaptic NMDA receptor clusters during
the first 2 weeks, indicating that none is essential for NMDA receptor
cluster formation. When NMDA receptor clusters became synaptic, PSD-95
and GKAP were always present, consistent with an essential function in
synaptic localization of NMDA receptors. Furthermore, PSD-95 and GKAP
clustered opposite presynaptic terminals several days before either
NMDA or AMPA receptors clustered at these presumptive postsynaptic
sites. These results suggest that synapse development proceeds by
formation of a postsynaptic scaffold containing PSD-95 and GKAP in
concert with presynaptic vesicle clustering, followed by regulated
attachment of glutamate receptor subtypes to this scaffold.
Key words:
NMDA receptor; AMPA receptor; PSD-95; PSD-93; PDZ domain; -actinin-2; chapsyn; GKAP; postsynaptic membrane; dendritic
spines
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841217-13$05.00/0
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[Full Text]
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N. Sans, R. S. Petralia, Y.-X. Wang, J. Blahos II, J. W. Hell, and R. J. Wenthold
A Developmental Change in NMDA Receptor-Associated Proteins at Hippocampal Synapses
J. Neurosci.,
February 1, 2000;
20(3):
1260 - 1271.
[Abstract]
[Full Text]
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J Meier, C Meunier-Durmort, C Forest, A Triller, and C Vannier
Formation of glycine receptor clusters and their accumulation at synapses
J. Cell Sci.,
January 8, 2000;
113(15):
2783 - 2795.
[Abstract]
[PDF]
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R. B. Nehring, E. Wischmeyer, F. Doring, R. W. Veh, M. Sheng, and A. Karschin
Neuronal Inwardly Rectifying K+ Channels Differentially Couple to PDZ Proteins of the PSD-95/SAP90 Family
J. Neurosci.,
January 1, 2000;
20(1):
156 - 162.
[Abstract]
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R. Tyzio, A. Represa, I. Jorquera, Y. Ben-Ari, H. Gozlan, and L. Aniksztejn
The Establishment of GABAergic and Glutamatergic Synapses on CA1 Pyramidal Neurons is Sequential and Correlates with the Development of the Apical Dendrite
J. Neurosci.,
December 1, 1999;
19(23):
10372 - 10382.
[Abstract]
[Full Text]
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M. Umemiya, M. Senda, and T. H Murphy
Behaviour of NMDA and AMPA receptor-mediated miniature EPSCs at rat cortical neuron synapses identified by calcium imaging
J. Physiol.,
November 15, 1999;
521(1):
113 - 122.
[Abstract]
[Full Text]
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Y.-P. Hsueh and M. Sheng
Regulated Expression and Subcellular Localization of Syndecan Heparan Sulfate Proteoglycans and the Syndecan-Binding Protein CASK/LIN-2 during Rat Brain Development
J. Neurosci.,
September 1, 1999;
19(17):
7415 - 7425.
[Abstract]
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G. Y. Ko and P. T. Kelly
Nitric Oxide Acts as a Postsynaptic Signaling Molecule in Calcium/Calmodulin-Induced Synaptic Potentiation in Hippocampal CA1 Pyramidal Neurons
J. Neurosci.,
August 15, 1999;
19(16):
6784 - 6794.
[Abstract]
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M. Wyszynski, J. G. Valtschanoff, S. Naisbitt, A. W. Dunah, E. Kim, D. G. Standaert, R. Weinberg, and M. Sheng
Association of AMPA Receptors with a Subset of Glutamate Receptor-Interacting Protein In Vivo
J. Neurosci.,
August 1, 1999;
19(15):
6528 - 6537.
[Abstract]
[Full Text]
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K. W. Roche, C. D. Ly, R. S. Petralia, Y.-X. Wang, A. W. McGee, D. S. Bredt, and R. J. Wenthold
Postsynaptic Density-93 Interacts with the delta 2 Glutamate Receptor Subunit at Parallel Fiber Synapses
J. Neurosci.,
May 15, 1999;
19(10):
3926 - 3934.
[Abstract]
[Full Text]
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K. R. Tovar and G. L. Westbrook
The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal Synapses In Vitro
J. Neurosci.,
May 15, 1999;
19(10):
4180 - 4188.
[Abstract]
[Full Text]
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R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis
The Glutamate Receptor Ion Channels
Pharmacol. Rev.,
March 1, 1999;
51(1):
7 - 62.
[Abstract]
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J.-Y. Song, K. Ichtchenko, T. C. Sudhof, and N. Brose
Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses
PNAS,
February 2, 1999;
96(3):
1100 - 1105.
[Abstract]
[Full Text]
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A Ghavami, K. Stark, M Jareb, S Ramboz, L Segu, and R Hen
Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons
J. Cell Sci.,
January 3, 1999;
112(6):
967 - 976.
[Abstract]
[PDF]
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W. Zhang, L. Vazquez, M. Apperson, and M. B. Kennedy
Citron Binds to PSD-95 at Glutamatergic Synapses on Inhibitory Neurons in the Hippocampus
J. Neurosci.,
January 1, 1999;
19(1):
96 - 108.
[Abstract]
[Full Text]
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H.-M. Zhao, R. J. Wenthold, and R. S. Petralia
Glutamate Receptor Targeting to Synaptic Populations on Purkinje Cells Is Developmentally Regulated
J. Neurosci.,
July 15, 1998;
18(14):
5517 - 5528.
[Abstract]
[Full Text]
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D. W. Allison, V. I. Gelfand, I. Spector, and A. M. Craig
Role of Actin in Anchoring Postsynaptic Receptors in Cultured Hippocampal Neurons: Differential Attachment of NMDA versus AMPA Receptors
J. Neurosci.,
April 1, 1998;
18(7):
2423 - 2436.
[Abstract]
[Full Text]
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A. E. El-Husseini, J. R. Topinka, J. E. Lehrer-Graiwer, B. L. Firestein, S. E. Craven, C. Aoki, and D. S. Bredt
Ion Channel Clustering by Membrane-associated Guanylate Kinases. DIFFERENTIAL REGULATION BY N-TERMINAL LIPID AND METAL BINDING MOTIFS
J. Biol. Chem.,
July 28, 2000;
275(31):
23904 - 23910.
[Abstract]
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