Cited by 590Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNicotinic Acetylcholine Receptors Study

The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking

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Bats, Cecile, Groc, Laurent, Choquet, Daniel·2007·Neuron

Abstract

Accumulation of AMPA receptors at synapses is a fundamental feature of glutamatergic synaptic transmission. Stargazin, a member of the TARP family, is an AMPAR auxiliary subunit allowing interaction of the receptor with scaffold proteins of the postsynaptic density, such as PSD-95. How PSD-95 and Stargazin regulate AMPAR number in synaptic membranes remains elusive. We show, using single quantum dot and FRAP imaging in live hippocampal neurons, that exchange of AMPAR by lateral diffusion between extrasynaptic and synaptic sites mostly depends on the interaction of Stargazin with PSD-95 and not upon the GluR2 AMPAR subunit C terminus. Disruption of interactions between Stargazin and PSD-95 strongly increases AMPAR surface diffusion, preventing AMPAR accumulation at postsynaptic sites. Furthermore, AMPARs and Stargazin diffuse as complexes in and out synapses. These results propose a model in which the Stargazin-PSD-95 interaction plays a key role to trap and transiently stabilize diffusing AMPARs in the postsynaptic density.

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Crossref · 10.1016/j.neuron.2007.01.030

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  • TARPs stabilize AMPARs both on the cell surface and at synapses, and loss of TARPs results in decreased AMPAR expression, suggesting TARPless AMPARs become unstable.

    “TARPs have been shown to stabilize AMPARs both on the cell surface and at synapses (Bats et al., 2007, Sheng et al., 2018), and loss of TARPs results in decreased AMPAR expression, suggesting that “TARPless” AMPARs become unstable (Fukaya et al., 2006, Chen et al., 2000).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Bats et al., 2007

  • Phosphorylation of the TARP C-terminus reduces interaction with membrane lipids and facilitates interaction with PSD95, serving to trap the TARP/AMPAR complex with the PSD.

    “Phosphorylation reduces the interaction with membrane lipids and facilitates interaction with PSD95, serving to trap the TARP/AMPAR complex with the PSD (Opazo et al., 2012, Bats et al., 2007, Sheng et al., 2018).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Bats et al., 2007

  • QD-labelled GluA2SEP receptors are less mobile inside synaptic clusters than outside, indicating confined motion at synapses.

    “QD-labelled GluA2SEP receptors were less mobile when inside synaptic clusters (Din=0.023 μm2 s−1, Dout=0.057 μm2 s−1 where D is the median diffusion coefficient, P<0.0001, Supplementary Figures 5C and D), indicating confined motion at synapses, as previously shown.46”

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Authors
Bats, C., Groc, L., & Choquet, D.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Choquet, Daniel
Venue
Neuron
Publisher
Elsevier BV
Published
2007-03
Volume
53
Issue
5
Pages
719-734
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1994778254
Cited by
590
References
10
Citations by year
2026: 16 · 2025: 10 · 2024: 30 · 2023: 17 · 2022: 21 · 2021: 39 · 2020: 22 · 2019: 29 · 2018: 48 · 2017: 30 · 2016: 28 · 2015: 23 · 2014: 39 · 2013: 37 · 2012: 36
FWCI
17.65
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
stargazin, PSD-95, AMPA receptors, postsynaptic density, extrasynaptic receptors, hippocampal neurons, glutamatergic synapses
MeSH terms
Disks Large Homolog 4 Protein, Animals, Cells, Cultured, Hippocampus, Membrane Proteins, Neurons, Protein Binding, Receptor Aggregation, Recombinant Proteins, Synapses, Calcium Channels, Gene Expression, Receptors, AMPA, Excitatory Postsynaptic Potentials, Protein Transport, Fluorescence Recovery After Photobleaching, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins, Mice, Guanylate Kinases

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