MAGUKs are essential, but redundant, in long-term potentiation
Open accessAbstract
This study presents evidence that the MAGUK family of synaptic scaffolding proteins plays an essential, but redundant, role in long-term potentiation (LTP). The action of PSD-95, but not that of SAP102, requires the binding to the transsynaptic adhesion protein ADAM22, which is required for nanocolumn stabilization. Based on these and previous results, we propose a two-step process in the recruitment of AMPARs during LTP. First, AMPARs, via TARPs, bind to exposed PSD-95 in the PSD. This alone is not adequate to enhance synaptic transmission. Second, the AMPAR/TARP/PSD-95 complex is stabilized in the nanocolumn by binding to ADAM22. A second, ADAM22-independent pathway is proposed for SAP102.
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AMPARs form discrete clusters scattered around the PSD.
“AMPARs form discrete clusters scattered around the PSD (256–259).”
From Synaptic memory and CaMKII (2023) · cites this paper as [259]
Activity-dependent synaptic recruitment of AMPARs may involve two steps: delivery to the PSD, then addition to AMPAR clusters in the nanocolumn.
“It is suggested that activity-dependent synaptic recruitment of AMPARs may involve two steps (259, 261). First, AMPARs are delivered to the PSD, but this is not enough to increase synaptic strength. Second, the newly recruited AMPARs are added to AMPAR clusters in the nanocolumn.”
From Synaptic memory and CaMKII (2023) · cites this paper as [259]
Cites
Stargazin 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 · see citing works
Self-citationThe AMPA Receptor Code of Synaptic Plasticity
Diering, G. H., & Huganir, R. L. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.018 · Cited by 844 · see citing works
A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Tang, A.-H., Chen, H., Li, T. P., Metzbower, S. R., MacGillavry, H. D., & Blanpied, T. A. (2016) · Nature · doi:10.1038/nature19058 · Cited by 677 · see citing works
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 · see citing works
Self-citationProtein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization
Takahashi, H., & Craig, A. M. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.06.002 · Cited by 257 · see citing works
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Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“However, it is important to keep in mind that redundancy exists among MAGUKs in their role in LTP (259).”
BackgroundInfluentialSelf-citation
- Authors
- Chen, X., Fukata, Y., Fukata, M., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- National Institutes of Natural Sciences (JP)
- Corresponding author
- Nicoll, Roger A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-07-09
- Volume
- 118
- Issue
- 28
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8285982
- OpenAlex
- W3181637521
- Cited by
- 16
- References
- 5
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (17H06413, 19K22439, 19K22548, 20H00459, 19H03331, 21K19390)
- National Institute of Mental Health (R01MH117139)
- 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 › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- long-term potentiation, PSD-95, SAP102, ADAM22, TARP, synaptic scaffolding, synaptic transmission
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Membrane Proteins, Models, Biological, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Protein Transport, Mice, Guanylate Kinases
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