Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
Open accessAbstract
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition. Furthermore, AMPAR assembly, trafficking, and functional heterogeneity depends on a large repertoire of auxiliary subunits-a feature that is particularly striking for this type of iGluR. Here, we discuss how the subunit structure, stoichiometry, and auxiliary subunits generate a heterogeneous plethora of receptors, each tailored to fulfill a vital role in fast synaptic signaling and plasticity.
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Binding of AMPAR/TARPs to PSD-95 is important for synaptic targeting and LTP.
“Since the binding of AMPAR/TARPs to the PSD protein PSD-95 is known to be important for synaptic targeting and LTP (278, 279)”
From Synaptic memory and CaMKII (2023) · cites this paper as [278]
AMPARs are decorated by auxiliary subunits that control their synthesis, trafficking, and biophysical properties.
“Evidence has accumulated over the past decade indicating that AMPARs are not stand-alone receptors; rather, they are decorated by numerous types of auxiliary subunits that control the synthesis, trafficking, and biophysical properties of these receptors (278–281).”
From Synaptic memory and CaMKII (2023) · cites this paper as [278]
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 [278]
Cites
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
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
Control of Kinetic Properties of AMPA Receptor Channels by Nuclear RNA Editing
Lomeli, H., Mosbacher, J., Melcher, T., Höger, T., Geiger, J. R. P., Kuner, T., Monyer, H., Higuchi, M., Bach, A., & Seeburg, P. H. (1994) · Science · doi:10.1126/science.7992055 · Cited by 746 · 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 · cited 2× · see citing works
“accumulation of AMPARs in subsynaptic nanoclusters directly opposite presynaptic release sites (Nair et al., 2013; Tang et al., 2016), as previously hypothesized (Raghavachari and Lisman, 2004).”
Sia, G.-M., Béïque, J.-C., Rumbaugh, G., Cho, R., Worley, P. F., & Huganir, R. L. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.020 · Cited by 201 · see citing works
Properties of Quantal Transmission at CA1 Synapses
Raghavachari, S., & Lisman, J. E. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00258.2004 · Cited by 197 · see citing works
A three-step model for the synaptic recruitment of AMPA receptors
Opazo, P., & Choquet, D. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.08.014 · Cited by 190 · see citing works
Transsynaptic modulation of kainate receptor functions by C1q-like proteins
Matsuda, K., Budisantoso, T., Mitakidis, N., Sugaya, Y., Miura, E., Kakegawa, W., Yamasaki, M., Konno, K., Uchigashima, M., Abe, M., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.001 · Cited by 180 · see citing works
Presynaptic neuronal pentraxin receptor organizes excitatory and inhibitory synapses
Lee, S.-J., Wei, M., Zhang, C., Maxeiner, S., Pak, C., Calado Botelho, S., Trotter, J., Sterky, F. H., & Südhof, T. C. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2768-16.2016 · Cited by 146 · see citing works
Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain
Watson, J. F., Ho, H., & Greger, I. H. (2017) · eLife · doi:10.7554/elife.23024 · Cited by 117 · see citing works
Self-citationGutierrez-Castellanos, N., Da Silva-Matos, C. M., Zhou, K., Canto, C. B., Renner, M. C., Koene, L. M. C., Ozyildirim, O., Sprengel, R., Kessels, H. W., & De Zeeuw, C. I. (2017) · Neuron · doi:10.1016/j.neuron.2016.11.046 · Cited by 111 · see citing works
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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Self-citationNicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“Since the binding of AMPAR/TARPs to the PSD protein PSD-95 is known to be important for synaptic targeting and LTP (278, 279), controlling this binding and/or the availability of PSD-95 is an obvious scenario.”
BackgroundSheng, N., Bemben, M. A., Díaz-Alonso, J., Tao, W., Shi, Y. S., & Nicoll, R. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800719115 · Cited by 65 · see citing works
Kadriu, B., Musazzi, L., Johnston, J. N., Kalynchuk, L. E., Caruncho, H. J., Popoli, M., & Zarate, C. A. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.07.027 · Cited by 62 · see citing works
Singh, A., Allen, D., Fracassi, A., Tumurbaatar, B., Natarajan, C., Scaduto, P., Woltjer, R., Kayed, R., Limon, A., Krishnan, B., et al. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200716 · Cited by 56 · see citing works
Davies, B., Brown, L. A., Cais, O., Watson, J., Clayton, A. J., Chang, V. T., Biggs, D., Preece, C., Hernandez-Pliego, P., Krohn, J., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx270 · Cited by 48 · see citing works
Self-citationKetamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors
Zaytseva, A., Bouckova, E., Wiles, M. J., Wustrau, M. H., Schmidt, I. G., Mendez-Vazquez, H., Khatri, L., & Kim, S. (2023) · eLife · doi:10.7554/elife.86022 · Cited by 48 · see citing works
Coombs, I. D., Ziobro, J., Krotov, V., Surtees, T., Cull‐Candy, S. G., & Farrant, M. (2022) · Epilepsia · doi:10.1111/epi.17419 · Cited by 32 · see citing works
Self-citationThe postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks
Sun, R., Allen, J. P., Mao, Z., Wilson, L., Haider, M., Alten, B., Zhou, Z., Wang, X., & Zhou, Q. (2025) · Journal of Cell Biology · doi:10.1083/jcb.202406133 · Cited by 20 · see citing works
- Authors
- Greger, I. H., Watson, J. F., & Cull-Candy, S. G.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University College London (GB)
- Corresponding author
- Greger, Ingo H.
- Cull-Candy, Stuart G.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 94
- Issue
- 4
- Pages
- 713-730
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2615999711
- Cited by
- 392
- References
- 12
- Citations by year
- 2026: 32 · 2025: 37 · 2024: 46 · 2023: 46 · 2022: 44 · 2021: 62 · 2020: 34 · 2019: 39 · 2018: 42 · 2017: 10
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- MRC (MR/J002976/1, MR/J012998/1, MC_U105174197)
- Wellcome Trust (086185/Z/08/Z)
- BBSRC (BB/N002113/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- AMPA receptors, ionotropic glutamate receptors, auxiliary subunits, receptor biogenesis, RNA editing, alternative splicing, post-translational modification, subunit stoichiometry, receptor trafficking, synaptic plasticity, excitatory neurotransmission
- MeSH terms
- Animals, Humans, Synaptic Transmission, Neuronal Plasticity, Protein Processing, Post-Translational, RNA Processing, Post-Transcriptional, Receptors, AMPA, Glutamic Acid, Protein Isoforms, Protein Subunits, Protein Transport
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