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Cited by 25Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsTreatment of Major Depression

Long-term potentiation reconstituted with an artificial TARP/PSD-95 complex

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Ravi, Anagh Sinha, Zeng, Menglong, Chen, Xudong, Sandoval, Gerardo, Diaz-Alonso, Javier, Zhang, Mingjie, Nicoll, Roger A.·2022·Cell Reports
DOI 10.1016/j.celrep.2022.111483PMC PMC9797105
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Abstract

The critical role of AMPA receptor (AMPAR) trafficking in long-term potentiation (LTP) of excitatory synaptic transmission is now well established, but the underlying molecular mechanism is still uncertain. Recent research suggests that PSD-95 captures AMPARs via an interaction with the AMPAR auxiliary subunits-transmembrane AMPAR regulatory proteins (TARPs). To determine if such interaction is a core minimal component of the AMPAR trafficking and LTP mechanism, we engineered artificial binding partners, which individually were biochemically and functionally dead but which, when expressed together, rescue binding and both basal synaptic transmission and LTP. These findings establish the TARP/PSD-95 complex as an essential interaction underlying AMPAR trafficking and LTP.

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Crossref · 10.1016/j.celrep.2022.111483

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  • Delivery of AMPARs to synapses requires binding of TARPs via their PDZ binding motifs to PSD-95.

    “It is now well established that the delivery of AMPARs to synapses requires the binding of TARPs, via their PDZ binding motifs (PBMs), to PSD-95 (278, 279, 286, 289, 294).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [294]

    The Discussion identifies TARP PBM binding to PSD-95 as a main requisite for synaptic AMPAR trafficking. But the Limitations of the study notes that roughly 35% of synaptic transmission may be TARP independent, so the unqualified claim that AMPAR delivery requires this interaction is broader than the paper establishes. Page numbers were not provided in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Synaptic capture of AMPARs requires the PDZ domain interaction between TARPs and PSD-95.

    “It is also agreed that the synaptic capture of AMPARs requires the PDZ domain interaction between TARPs and PSD-95 (275, 279, 294, 440).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [294]

    The Discussion reports that a functional TARP PBM–PSD-95 PDZ interaction is necessary for TARP-assisted AMPAR accumulation at synapses. Its Limitations section narrows that conclusion to the TARP γ-8-based trafficking studied and notes that some synaptic transmission may be TARP independent. The unqualified claim that synaptic capture of AMPARs requires this interaction therefore goes beyond the paper's findings. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cites

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Cited by

Sorted by citations

Authors
Ravi, A. S., Zeng, M., Chen, X., Sandoval, G., Diaz-Alonso, J., Zhang, M., & Nicoll, R. A.
Affiliations
  • University of California, San Francisco (US)
  • Hong Kong University of Science and Technology (HK)
  • University of California, Irvine (US)
Corresponding author
Nicoll, Roger A.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2022-10
Volume
41
Issue
2
Pages
111483
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2022.111483
PMC
PMC9797105
OpenAlex
W4304196195
Cited by
25
References
6
Citations by year
2026: 7 · 2025: 6 · 2024: 6 · 2023: 6
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • National Institutes of Health (K99/R00 MH118425, R01MH070957, R01MH117139)
  • Research Grants Council, University Grants Committee (16101419, AoE-M09-12)
  • Shenzhen Bay Laboratory (S201101002)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
long-term potentiation, AMPA receptor trafficking, TARP, PSD-95, transmembrane AMPA receptor regulatory proteins, excitatory synaptic transmission, synaptic plasticity
MeSH terms
Disks Large Homolog 4 Protein, Synaptic Transmission, Nuclear Proteins, Synapses, Long-Term Potentiation, Receptors, AMPA

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