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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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Cites
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951
PEST sequences and regulation by proteolysis
Rechsteiner, M., & Rogers, S. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10031-1 · Cited by 1,707
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420 · cited 2×
“We cotransfected from mice lacking Mdm2 (Montes de Oca Luna et al., 1995).”
Synaptic plasticity: LTP and LTD
Bear, M. F., & Malenka, R. C. (1994) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(94)90101-5 · Cited by 1,355
Self-citationPSD-95 Involvement in Maturation of Excitatory Synapses
El-Husseini, A. E.-D., Schnell, E., Chetkovich, D. M., Nicoll, R. A., & Bredt, D. S. (2000) · Science · doi:10.1126/science.290.5495.1364 · Cited by 1,303
Migaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G. M., Morrison, J. H., et al. (1998) · Nature · doi:10.1038/24790 · Cited by 1,160
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity
Lee, H.-K., Barbarosie, M., Kameyama, K., Bear, M. F., & Huganir, R. L. (2000) · Nature · doi:10.1038/35016089 · Cited by 1,116
Self-citationStargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
Chen, L., Chetkovich, D. M., Petralia, R. S., Sweeney, N. T., Kawasaki, Y., Wenthold, R. J., Bredt, D. S., & Nicoll, R. A. (2000) · Nature · doi:10.1038/35050030 · Cited by 1,111
Reinsertion or Degradation of AMPA Receptors Determined by Activity-Dependent Endocytic Sorting
Ehlers, M. D. (2000) · Neuron · doi:10.1016/s0896-6273(00)00129-x · Cited by 1,096
Shi, S.-H., Hayashi, Y., Esteban, J. A., & Malinow, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00321-x · Cited by 1,094
Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression
Mulkey, R. M., Endo, S., Shenolikar, S., & Malenka, R. C. (1994) · Nature · doi:10.1038/369486a0 · Cited by 1,083
Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system
Ehlers, M. D. (2003) · Nature Neuroscience · doi:10.1038/nn1013 · Cited by 977
Lu, W.-Y., Man, H., Ju, W. H., Trimble, W. S., MacDonald, J. F., & Wang, Y. T. (2001) · Neuron · doi:10.1016/s0896-6273(01)00194-5 · Cited by 935
Jiang, Y.-H., Armstrong, D., Albrecht, U., Atkins, C. M., Noebels, J. L., Eichele, G., Sweatt, J. D., & Beaudet, A. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80596-6 · Cited by 852
Xia, Z., Dudek, H., Miranti, C. K., & Greenberg, M. E. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-17-05425.1996 · Cited by 787
Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number
Schnell, E., Sizemore, M., Karimzadegan, S., Chen, L., Bredt, D. S., & Nicoll, R. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172511199 · Cited by 775
Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD
Beattie, E. C., Carroll, R. C., Yu, X., Morishita, W., Yasuda, H., von Zastrow, M., & Malenka, R. C. (2000) · Nature Neuroscience · doi:10.1038/81823 · Cited by 745
Man, H., Lin, J., Ju, W. H., Ahmadian, G., Liu, L., Becker, L. E., Sheng, M., & Wang, Y. T. (2000) · Neuron · doi:10.1016/s0896-6273(00)81067-3 · Cited by 711
Mapping of the p53 and mdm-2 Interaction Domains
Chen, J., Maréchal, V., & Levine, A. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.7.4107 · Cited by 700
Role of AMPA Receptor Cycling in Synaptic Transmission and Plasticity
Lüscher, C., Xia, H., Beattie, E. C., Carroll, R. C., von Zastrow, M., Malenka, R. C., & Nicoll, R. A. (1999) · Neuron · doi:10.1016/s0896-6273(00)81119-8 · Cited by 692
Unusual spectral energy distribution of a galaxy previously reported to be at redshift 6.68
Chen, H., Lanzetta, K. M., Pascarelle, S. M., & Yahata, N. (2000) · RePEc: Research Papers in Economics · Cited by 680
Lee, H.-K., Kameyama, K., Huganir, R. L., & Bear, M. F. (1998) · Neuron · doi:10.1016/s0896-6273(00)80632-7 · Cited by 668
Self-citationSherr, C. J., & Weber, J. D. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00038-6 · Cited by 654
Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase
Banke, T. G., Bowie, D., Lee, H.-K., Huganir, R. L., Schousboe, A., & Traynelis, S. F. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00089.2000 · Cited by 652
Synaptic Strength Regulated by Palmitate Cycling on PSD-95
El-Husseini, A., Schnell, E., Dakoji, S., Sweeney, N. T., Zhou, Q., Prange, O., Gauthier-Campbell, C., Aguilera-Moreno, A., Nicoll, R. A., & Bredt, D. S. (2002) · Cell · doi:10.1016/s0092-8674(02)00683-9 · Cited by 569
Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization
Lin, J., Ju, W. H., Foster, K. A., Lee, S. H., Ahmadian, G., Wyszynski, M. W., Wang, Y. T., & Sheng, M. (2000) · Nature Neuroscience · doi:10.1038/81814 · Cited by 562
Internalization of ionotropic glutamate receptors in response to mGluR activation
Snyder, E. M., Philpot, B. D., Huber, K. M., Dong, X., Fallon, J. R., & Bear, M. F. (2001) · Nature Neuroscience · doi:10.1038/nn746 · Cited by 539
Self-citationZeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B. D., Miyakawa, T., Bear, M. F., & Tonegawa, S. (2001) · Cell · doi:10.1016/s0092-8674(01)00585-2 · Cited by 498
Self-citationTargeting of PKA to Glutamate Receptors through a MAGUK-AKAP Complex
Colledge, M., Dean, R. A., Scott, G. K., Langeberg, L. K., Huganir, R. L., & Scott, J. D. (2000) · Neuron · doi:10.1016/s0896-6273(00)00013-1 · Cited by 467
Self-citationPickart, C. M. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01681-9 · Cited by 458
Unusual spectral energy distribution of a galaxy previously reported to be at redshift 6.68
Chen, H., Lanzetta, K. M., Pascarelle, S., & Yahata, N. (2000) · Nature · doi:10.1038/35046031 · Cited by 447
Dynamin-dependent endocytosis of ionotropic glutamate receptors
Carroll, R. C., Beattie, E. C., Xia, H., Lüscher, C., Altschuler, Y., Nicoll, R. A., Malenka, R. C., & von Zastrow, M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.14112 · Cited by 423
Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons
Liao, D., Zhang, X., O’Brien, R., Ehlers, M., & Huganir, R. L. (1999) · Nature Neuroscience · doi:10.1038/4540 · Cited by 396
Ubiquitination-dependent mechanisms regulate synaptic growth and function
DiAntonio, A., Haghighi, A. P., Portman, S. L., Lee, J. D., Amaranto, A. M., & Goodman, C. S. (2001) · Nature · doi:10.1038/35086595 · Cited by 383
Rosenmund, C., Carr, D. W., Bergeson, S. E., Nilaver, G., Scott, J. D., & Westbrook, G. L. (1994) · Nature · doi:10.1038/368853a0 · Cited by 371
Self-citationHegde, A. N., Inokuchi, K., Pei, W., Casadio, A., Ghirardi, M., Chain, D. G., Martin, K. C., Kandel, E. R., & Schwartz, J. H. (1997) · Cell · doi:10.1016/s0092-8674(00)80188-9 · Cited by 356
Molecular organization of the postsynaptic specialization
Sheng, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111146298 · Cited by 343
Stein, V., House, D. R. C., Bredt, D. S., & Nicoll, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05503.2003 · Cited by 341
PSD‐95 regulates synaptic transmission and plasticity in rat cerebral cortex
Béïque, J.-C., & Andrade, R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.031369 · Cited by 312
Gardiol, D., Kühne, C., Glaunsinger, B. A., Lee, S. S., Javier, R., & Banks, L. (1999) · Oncogene · doi:10.1038/sj.onc.1202920 · Cited by 303
Glaunsinger, B. A., Lee, S. S., Thomas, M., Banks, L., & Javier, R. T. (2000) · Oncogene · doi:10.1038/sj.onc.1203906 · Cited by 297
Burbea, M., Dreier, L., Dittman, J. S., Grunwald, M. E., & Kaplan, J. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00749-3 · Cited by 294
Kameyama, K., Lee, H.-K., Bear, M. F., & Huganir, R. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80633-9 · Cited by 283
Self-citationLee, S. S., Glaunsinger, B. A., Mantovani, F., Banks, L., & Javier, R. T. (2000) · Journal of Virology · doi:10.1128/jvi.74.20.9680-9693.2000 · Cited by 266
Wilson, S. M., Bhattacharyya, B. J., Rachel, R. A., Coppola, V., Tessarollo, L., Householder, D. B., Fletcher, C., Miller, R. J., Copeland, N. G., & Jenkins, N. A. (2002) · Nature Genetics · doi:10.1038/ng1006 · Cited by 264
The Ubiquitin Proteasome System Acutely Regulates Presynaptic Protein Turnover and Synaptic Efficacy
Speese, S. D., Trotta, N., Rodesch, C. K., Aravamudan, B., & Broadie, K. S. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00338-5 · Cited by 236
The ubiquitin–proteasome cascade is required for mammalian long‐term memory formation
Lopez‐Salon, M., Alonso, M., Vianna, M. R. M., Viola, H., E Souza, T. M., Izquierdo, I., Pasquini, J. M., & Medina, J. H. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01806.x · Cited by 224
Tavalin, S. J., Colledge, M., Hell, J. W., Langeberg, L. K., Huganir, R. L., & Scott, J. D. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03044.2002 · Cited by 222
Self-citationBidirectional, Activity-Dependent Regulation of Glutamate Receptors in the Adult Hippocampus In Vivo
Heynen, A. J., Quinlan, E. M., Bae, D. C., & Bear, M. F. (2000) · Neuron · doi:10.1016/s0896-6273(00)00130-6 · Cited by 213
Self-citationβ1-Adrenergic Receptor Association with PSD-95
Hu, L. A., Tang, Y., Miller, W. E., Cong, M., Lau, A. G., Lefkowitz, R. J., & Hall, R. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005938200 · Cited by 166
Hegde, A. N., & DiAntonio, A. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn961 · Cited by 158
Independent mechanisms for long-term depression of AMPA and NMDA responses.
Selig, D. K., Hjelmstad, G., Herron, C., Nicoll, R., & Malenka, R. (1995) · Neuron · doi:10.1016/0896-6273(95)90045-4 · Cited by 137
The Ubiquitin Proteasome System Functions as an Inhibitory Constraint on Synaptic Strengthening
Zhao, Y., Hegde, A. N., & Martin, K. C. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00332-4 · Cited by 136
Oliveria, S. F., Gomez, L. L., & Dell'Acqua, M. L. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200209127 · Cited by 129
Dunah, A. W., Luo, J., Wang, Y., Yasuda, R. P., & Wolfe, B. B. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.3.429 · Cited by 127
Eye opening induces a rapid dendritic localization of PSD-95 in central visual neurons
Yoshii, A., Sheng, M., & Constantine‐Paton, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0335785100 · Cited by 111
Internalization of the Kv1.4 Potassium Channel Is Suppressed by Clustering Interactions with PSD-95
Jugloff, D. G. M., Khanna, R., Schlichter, L. C., & Jones, O. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.2.1357 · Cited by 104
New Roles for Ubiquitin in the Assembly and Function of Neuronal Circuits
Murphey, R. K., & Godenschwege, T. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00943-1 · Cited by 72
A Role of the Ubiquitin–Proteasome System in Neuropathic Pain
Moss, A., Blackburn-Munro, G., Garry, E. M., Blakemore, J., Dickinson, T., Rosie, R., Mitchell, R., & Fleetwood-Walker, S. M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-04-01363.2002 · Cited by 62
Ubiquitin-mediated proteolysis in learning and memory
Chain, D. G., Schwartz, J. H., & Hegde, A. N. (1999) · Molecular Neurobiology · doi:10.1007/bf02742438 · Cited by 61
Ubiquitination--More Than Two to Tango
Joazeiro, C. A. P., & Hunter, T. R. (2000) · Science · doi:10.1126/science.289.5487.2061 · Cited by 41
Malinow, R., & Malenka, R. C. (2002) · Cited by 1
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Citri, A., & Malenka, R. C. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301559 · Cited by 2,323
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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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