A developmental change in NMDA receptor-associated proteins at hippocampal synapses
Open accessAbstract
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.
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PSD95 and NR1 rise due to the robust synaptogenesis that occurs during this time.
“which rise due to the robust synaptogenesis that occurs during this time (Sans et al., 2000).”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Sans et al., 2000
The Results section (‘Development of PSD-95/SAP-102 proteins at the synapse’; page unavailable) reports that synaptic PSD-95 increases during development. The Discussion attributes this mainly to more synapses containing PSD-95, not to demonstrated synaptogenesis; it treats formation of new synapses as an alternative explanation. The cited passages do not establish a developmental rise in NR1. (LLM, conf=0.86)
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- Vaughn JE (1989) Review: fine structure of synaptogenesis in the ver- tebrate central nervous system. Synapse 3:255-285.
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Self-citation
- Authors
- Sans, N., Petralia, R. S., Wang, Y.-X., Blahos, J., Hell, J. W., & Wenthold, R. J.
- Affiliations
- National Institutes of Health (US)
- University of Wisconsin–Madison (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-02-01
- Volume
- 20
- Issue
- 3
- Pages
- 1260-1271
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6774158
- OpenAlex
- W1648575050
- Cited by
- 537
- References
- 0
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 11 · 2023: 9 · 2022: 9 · 2021: 17 · 2020: 16 · 2019: 21 · 2018: 19 · 2017: 20 · 2016: 17 · 2015: 19 · 2014: 23 · 2013: 20 · 2012: 27
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders
- National Institute of Neurological Disorders and Stroke (R01NS035563, NS 35563)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- NMDA receptor, synaptic development, hippocampus, PSD-95, PSD-93, NR2A, NR2B, synaptic proteins, postsynaptic density, CA1 synapses, postnatal development
- MeSH terms
- Disks Large Homolog 4 Protein, Aging, Animals, Cell Line, Hippocampus, Humans, Immunohistochemistry, Membrane Proteins, Nerve Tissue Proteins, Neuropeptides, Nuclear Proteins, Nucleoside-Phosphate Kinase, Synapses, Transcription Factors, Blotting, Western, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Receptors, AMPA, Protein Isoforms, Intracellular Signaling Peptides and Proteins, Rats, Guanylate Kinases
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