The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Ubiquitination Regulates PSD-95 Degradation and AMPA Receptor Surface Expression
Open accessAbstract
PSD-95 is a major scaffolding protein of the postsynaptic density, tethering NMDA- and AMPA-type glutamate receptors to signaling proteins and the neuronal cytoskeleton. Here we show that PSD-95 is regulated by the ubiquitin-proteasome pathway. PSD-95 interacts with and is ubiquitinated by the E3 ligase Mdm2. In response to NMDA receptor activation, PSD-95 is ubiquitinated and rapidly removed from synaptic sites by proteasome-dependent degradation. Mutations that block PSD-95 ubiquitination prevent NMDA-induced AMPA receptor endocytosis. Likewise, proteasome inhibitors prevent NMDA-induced AMPA receptor internalization and synaptically induced long-term depression. This is consistent with the notion that PSD-95 levels are an important determinant of AMPA receptor number at the synapse. These data suggest that ubiquitination of PSD-95 through an Mdm2-mediated pathway is critical in regulating AMPA receptor surface expression during synaptic plasticity.
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“GluA1 phosphorylation directly regulates trafficking, but there are other phosphatase substrates, including PSD-95 and Stargazin, that are also involved in synaptic AMPAR removal during LTD.”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca2+-Permeable AMPA Receptors (2012) · cites this paper as Colledge et al., 2003
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“In particular, NMDA-cLTD activation of CaN and PP1/2A negatively regulates PSD-95 postsynaptic clustering and binding to Stargazin to promote AMPAR removal”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca2+-Permeable AMPA Receptors (2012) · cites this paper as Colledge et al., 2003
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Metadata
- Authors
- Colledge, M., Snyder, E. M., Crozier, R. A., Soderling, J. A., Jin, Y., Langeberg, L. K., Lu, H., Bear, M. F., & Scott, J. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Oregon Health & Science University (US)
- Corresponding author
- Scott, John D.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 40
- Issue
- 3
- Pages
- 595-607
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3963808
- OpenAlex
- W2151538478
- Cited by
- 567
- References
- 65
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 20 · 2023: 11 · 2022: 12 · 2021: 24 · 2020: 20 · 2019: 23 · 2018: 18 · 2017: 21 · 2016: 20 · 2015: 36 · 2014: 22 · 2013: 30 · 2012: 26
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM048231, GM-48231, R37GM048231)
- National Institute of Neurological Disorders and Stroke (NS 39321, P01NS039321)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- PSD-95, ubiquitination, MDM2, proteasomal degradation, AMPA receptors, receptor internalization, NMDA receptor activation, postsynaptic density, synaptic plasticity, long-term depression, glutamate receptors
- MeSH terms
- Disks Large Homolog 4 Protein, Acetylcysteine, Analysis of Variance, Animals, Animals, Newborn, Epitopes, Calcium, Cells, Cultured, Drug Interactions, Electric Stimulation, Embryo, Mammalian, Endocytosis, Colforsin, Hippocampus, Humans, Immunoglobulin G, Immunohistochemistry, Immunosuppressive Agents, Kidney, Leupeptins, Membrane Potentials, Membrane Proteins, Mutation, Nerve Tissue Proteins, Neural Inhibition, Neurons, Nuclear Proteins, Proto-Oncogene Proteins, Synapses, Time Factors, Transfection, Blotting, Western, Cysteine Proteinase Inhibitors, N-Methylaspartate, Tacrolimus, Synapsins, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, Rats, Long-Evans, Ubiquitin, Intracellular Signaling Peptides and Proteins, Rats, Proto-Oncogene Proteins c-mdm2, In Vitro Techniques
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