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Subunit-Specific NMDA Receptor Trafficking to Synapses
Open accessAbstract
To elucidate mechanisms controlling the number and subunit composition of synaptic NMDA-Rs in hippocampal slice neurons, the NR1, NR2A, and NR2B subunits were optically and electrophysiologically tagged. The NR2 subunit directs delivery of receptors to synapses with different rules controlling NR2A and NR2B. Synaptic incorporation of NR2B-containing receptors is not limited by synaptic transmission nor enhanced by increased subunit expression. NR2A-containing receptors whose expression normally increases with age replace synaptic NR2B-containing receptors. Replacement is enhanced by increased NR2A expression and requires synaptic activity. Surprisingly, spontaneously released transmitter acting on synaptic NMDA-Rs is sufficient for replacement and reduces NMDA-R responses. Thus, as with AMPA-Rs, synaptic trafficking of NMDA-Rs is tightly regulated and has subunit-specific rules with functionally important consequences.
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“The second approach utilizes mutations in the CTD of GluN2B that cannot bind CaMKII as replacement for the wt (CaMKII L1298A/R1300Q) (120, 121, 230) or either competing with overexpressed full-length constructs (GluN2B R1300S/Q1303D) (231) or competing by expressing just the wt GluN2B CTD (839–1482) (232). The results are highly variable as reviewed in Ref. 233, ranging from complete block of LTP”
From Synaptic memory and CaMKII (2023) · cites this paper as [231]
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Keith, R. E., Wild, G. A., Keith, M. J., Chen, D., Pack, S., & Dumas, T. C. (2024) · Synapse · doi:10.1002/syn.22292 · Cited by 11
Effects of NR2A and NR2B-containing N-methyl-D-aspartate receptors on neuronal-firing properties
Shi, M., Wu, X., Wei, C., Yang, M., Liu, Z., & Ren, W. (2011) · Neuroreport · doi:10.1097/wnr.0b013e32834ae32e · Cited by 8
Metadata
- Authors
- Barria, A., & Malinow, R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Malinow, Roberto
- ORCID
- Malinow, Roberto
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 35
- Issue
- 2
- Pages
- 345-353
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2030377743
- Cited by
- 515
- References
- 151
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 16 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 17 · 2019: 22 · 2018: 12 · 2017: 15 · 2016: 26 · 2015: 27 · 2014: 28 · 2013: 23 · 2012: 23
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4034 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- NMDA receptor, receptor trafficking, NR2A, NR2B, NR1, subunit composition, hippocampal neurons, spontaneous neurotransmission, receptor subunit expression, synaptic plasticity
- MeSH terms
- Animals, Animals, Newborn, Cell Compartmentation, Cells, Cultured, Dendrites, Dose-Response Relationship, Drug, Hippocampus, Indicators and Reagents, Luminescent Proteins, Membrane Potentials, Mutation, Synaptic Transmission, Organ Culture Techniques, Recombinant Fusion Proteins, Synapses, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Excitatory Amino Acid Antagonists, Protein Transport, Sodium Channel Blockers, Green Fluorescent Proteins
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