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NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders

Lau, C. Geoffrey, Zukin, R. Suzanne·2007·Nature Reviews Neuroscience

DOI 10.1038/nrn2153

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Abstract

The number and subunit composition of synaptic N-methyl-D-aspartate receptors (NMDARs) are not static, but change in a cell- and synapse-specific manner during development and in response to neuronal activity and sensory experience. Neuronal activity drives not only NMDAR synaptic targeting and incorporation, but also receptor retrieval, differential sorting into the endosomal-lysosomal pathway and lateral diffusion between synaptic and extrasynaptic sites. An emerging concept is that activity-dependent, bidirectional regulation of NMDAR trafficking provides a dynamic and potentially powerful mechanism for the regulation of synaptic efficacy and remodelling, which, if dysregulated, can contribute to neuropsychiatric disorders such as cocaine addiction, Alzheimer's disease and schizophrenia.

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Palmitoylation by DHHC5/8 Targets GRIP1 to Dendritic Endosomes to Regulate AMPA-R Trafficking
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Neto1 Is a Novel CUB-Domain NMDA Receptor–Interacting Protein Required for Synaptic Plasticity and Learning
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“complex and leads to the stabilization of receptors on the cell surface, increasing synaptic efficiency (for reviews see Kopp et al., 2007; Chen and Roche, 2007; Lau and Zukin, 2007).”
Background
N ‐Methyl‐ d ‐aspartate receptors are required for synaptic targeting of Alzheimer’s toxic amyloid‐β peptide oligomers
Decker, H., Jürgensen, S., Adrover, M. F., Brito‐Moreira, J., Bomfim, T. R., Klein, W. L., Epstein, A. L., Felice, F. G. D., Jerusalinsky, D. A., & Ferreira, S. T. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07058.x · Cited by 172
Cdk5 Regulates the Phosphorylation of Tyrosine 1472 NR2B and the Surface Expression of NMDA Receptors
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BackgroundInfluential
EphB Controls NMDA Receptor Function and Synaptic Targeting in a Subunit-Specific Manner
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Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression
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Identification of blood biomarkers for psychosis using convergent functional genomics
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AMPA receptors as drug targets in neurological disease—advantages, caveats, and future outlook
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Authors: Lau, C. G., & Zukin, R. S.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Zukin, R. Suzanne
ORCID: Lau, C. Geoffrey
Zukin, R. Suzanne
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2007-06
Volume: 8
Issue: 6
Pages: 413-426
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/nrn2153
OpenAlex: W1985241009
Cited by: 1,159
References: 154
Citations by year: 2026: 27 · 2025: 27 · 2024: 35 · 2023: 50 · 2022: 39 · 2021: 60 · 2020: 54 · 2019: 70 · 2018: 75 · 2017: 66 · 2016: 51 · 2015: 78 · 2014: 70 · 2013: 69 · 2012: 89
FWCI: 6.05
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Neurological Disorders and Stroke (NS-20752, R01NS020752)
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 › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords: NMDA receptor, receptor trafficking, synaptic plasticity, postsynaptic density, receptor subunit composition, synaptic targeting, endolysosomal pathway, extrasynaptic receptors, activity-dependent regulation, cocaine dependence, Alzheimer's disease, schizophrenia, neuropsychiatric disorders
MeSH terms: Animals, Mental Disorders, Brain, Endocytosis, Humans, Synaptic Transmission, Neuronal Plasticity, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Protein Transport

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NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders

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