Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase
Open accessAbstract
Modulation of postsynaptic AMPA receptors in the brain by phosphorylation may play a role in the expression of synaptic plasticity at central excitatory synapses. It is known from biochemical studies that GluR1 AMPA receptor subunits can be phosphorylated within their C terminal by cAMP-dependent protein kinase A (PKA), which is colocalized with the phosphatase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability (PO,PEAK), and single-channel properties of glutamateevoked responses for neuronal AMPA receptors and homomeric GluR1(flip) receptors recorded in outside-out patches. Inclusion of purified catalytic subunit Cα-PKA in the pipette solution increased neuronal AMPA receptor PO,PEAK(0.92) compared with recordings made with calcineurin included in the pipette (PO,PEAK 0.39). Similarly, Cα-PKA increased PO,PEAK for recombinant GluR1 receptors (0.78) compared with patches excised from cells cotransfected with a cDNA encoding the PKA peptide inhibitor PKI (PO,PEAK 0.50) or patches with calcineurin included in the pipette (PO,PEAK 0.42). Neither PKA nor calcineurin altered the amplitude of single-channel subconductance levels, weighted mean unitary current, mean channel open period, burst length, or macroscopic response waveform for recombinant GluR1 receptors. Substitution of an amino acid at the PKA phosphorylation site (S845A) on GluR1 eliminated the PKA-induced increase in PO,PEAK, whereas the mutation of a Ca 2+,calmodulin-dependent kinase II and PKC phosphorylation site (S831A) was without effect. These results suggest that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.
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Phosphorylation of AMPAR GluA1 subunits on S845 by PKA increases channel open probability and promotes receptor recycling and exocytosis at extrasynaptic sites near the postsynaptic density.
“Phosphorylation of AMPAR GluA1 (formerly GluR1) subunits on S845 by PKA increases channel open probability and promotes receptor recycling and exocytosis at extrasynaptic sites near the postsynaptic density (PSD)”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca<sup>2+</sup>-Permeable AMPA Receptors (2012) · cites this paper as Banke et al., 2000
The Discussion reports that PKA phosphorylation of GluR1 Ser845 appears to increase peak channel open probability. The paper does not establish the additional claim that this phosphorylation promotes receptor recycling or exocytosis at extrasynaptic sites near the PSD; the passages on receptor localization discuss it only as background. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPhosphorylation of S845 increases single channel open probability and promotes GluA1 targeting or retention to the cell surface.
“Phosphorylation of S845 increases single channel open–probability and also promotes GluA1 targeting or retention to the cell surface (Banke et al., 2000, Oh et al., 2006, Man et al., 2007).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Banke et al., 2000
The Discussion states that phosphorylation of GluR1 Ser845 by PKA appears to increase peak open probability, supporting the first part of the sentence. The passages on recombinant receptor function and the additional search do not establish that Ser845 phosphorylation promotes targeting or retention at the cell surface. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGluA1 T840 phosphorylation increases GluA1 single channel conductance, while phosphorylation of S845 increases channel open probability.
“GluA1 T840 phosphorylation has been shown to increase GluA1 single channel conductance while phosphorylation of S845 increases channel open probability, suggesting that dephosphorylation of these sites might also be important to reduce ion channel properties for expression of LTD (Banke et al., 2000, Jenkins et al., 2014).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Banke et al., 2000
The Discussion states that phosphorylation of GluR1 Ser845 increases peak open probability, supporting the S845 part of the claim. The paper does not address T840 phosphorylation or attribute increased single-channel conductance to T840; its Discussion instead associates increased unitary conductance with Ser831 phosphorylation. (LLM, conf=0.87)
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Cites
Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729 · see citing works
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 · see citing works
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 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Pearson RB, Kemp BE (1991) Protein kinase phosphorylation site se- quences and consensus specificity motifs: tabulations. Methods Enzy- mol 200A:62-81.
- Z ar JH (1999) Biostatistical analysis. Upper Saddle River, NJ: Prentice Hall.
Cited by
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Central sensitization: a generator of pain hypersensitivity by central neural plasticity
Latremoliere, A., & Woolf, C. J. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.06.012 · Cited by 3,913 · 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
Self-citationMechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
AKAP signalling complexes: focal points in space and time
Wong, W., & Scott, J. D. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1527 · Cited by 1,073 · see citing works
PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity
Esteban, J. A., Shi, S.-H., Wilson, C., Nuriya, M., Huganir, R. L., & Malinow, R. (2003) · Nature Neuroscience · doi:10.1038/nn997 · Cited by 894 · see citing works
Self-citationNeurobiology of relapse to heroin and cocaine seeking: a review
Shalev, U., Grimm, J. W., & Shaham, Y. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.1.1 · Cited by 880 · see citing works
The 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
Self-citationStructure, 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-citationRegulatory mechanisms of AMPA receptors in synaptic plasticity
Derkach, V. A., Oh, M. C., Guire, E. S., & Soderling, T. R. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2055 · Cited by 708 · see citing works
Ubiquitination Regulates PSD-95 Degradation and AMPA Receptor Surface Expression
Colledge, M., Snyder, E. M., Crozier, R. A., Soderling, J. A., Jin, Y., Langeberg, L. K., Lu, H., Bear, M. F., & Scott, J. D. (2003) · Neuron · doi:10.1016/s0896-6273(03)00687-1 · Cited by 567 · see citing works
Stargazin modulates AMPA receptor gating and trafficking by distinct domains
Tomita, S., Adesnik, H., Sekiguchi, M., Zhang, W., Wada, K., Howe, J. R., Nicoll, R. A., & Bredt, D. S. (2005) · Nature · doi:10.1038/nature03624 · Cited by 486 · see citing works
Emotion Enhances Learning via Norepinephrine Regulation of AMPA-Receptor Trafficking
Hu, H., Real, E., Takamiya, K., Kang, M.-G., Ledoux, J., Huganir, R. L., & Malinow, R. (2007) · Cell · doi:10.1016/j.cell.2007.09.017 · Cited by 496 · see citing works
Self-citationMan, H.-Y., Sekine-Aizawa, Y., & Huganir, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611698104 · Cited by 311 · see citing works
Self-citationSpine Expansion and Stabilization Associated with Long-Term Potentiation
Yang, Y., Wang, X.-B., Frerking, M., & Zhou, Q. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3998-07.2008 · Cited by 222 · see citing works
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Morishita, W., Connor, J. H., Xia, H., Quinlan, E. M., Shenolikar, S., & Malenka, R. C. (2001) · Neuron · doi:10.1016/s0896-6273(01)00554-2 · Cited by 227 · see citing works
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Qiu, S., Zhao, L. F., Korwek, K. M., & Weeber, E. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2561-06.2006 · Cited by 186 · see citing works
AKAP signaling complexes in regulation of excitatory synaptic plasticity
Sanderson, J. L., & Dell'Acqua, M. L. (2011) · The Neuroscientist · doi:10.1177/1073858410384740 · Cited by 185 · see citing works
Distinct enzyme combinations in AKAP signalling complexes permit functional diversity
Hoshi, N., Langeberg, L. K., & Scott, J. D. (2005) · Nature Cell Biology · doi:10.1038/ncb1315 · Cited by 183 · see citing works
Chan, C.-S., Weeber, E. J., Zong, L., Fuchs, E., Sweatt, J. D., & Davis, R. L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4110-05.2006 · Cited by 165 · see citing works
Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence
Allison, C., & Pratt, J. A. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00029-9 · Cited by 160 · see citing works
Sanderson, J. L., Gorski, J. A., Gibson, E. S., Lam, P., Freund, R. K., Chick, W. S., & Dell'Acqua, M. L. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3326-12.2012 · Cited by 137 · see citing works
“…protein kinase (PKA) increases channel open probability and promotes receptor recycling and exocytosis at extrasynaptic sites near the postsynaptic density (PSD) (Banke et al., 2000; Ehlers, 2000; Esteban et al., 2003; Oh et al., 2006; Man et al., 2007; Yang et al., 2008; He et al., 2009).”
BackgroundLin, H.-C., Mao, S.-C., & Gean, P.-W. (2006) · Learning & Memory · doi:10.1101/lm.217006 · Cited by 107 · see citing works
Goel, A., Xu, L. W., Snyder, K. P., Song, L., Goenaga-Vazquez, Y., Megill, A., Takamiya, K., Huganir, R. L., & Lee, H.-K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018264 · Cited by 103 · see citing works
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Maas, J. W., Vogt, S. K., Chan, G. C. K., Pineda, V. V., Storm, D. R., & Muglia, L. J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4273-04.2005 · Cited by 99 · see citing works
Cellular Receptors of Amyloid β Oligomers (AβOs) in Alzheimer’s Disease
Mroczko, B., Groblewska, M., Litman-Zawadzka, A., Kornhuber, J., & Lewczuk, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071884 · Cited by 97 · see citing works
Lopes, M. W., Soares, F. M. S., de Mello, N., Nunes, J. C., Cajado, A. G., de Brito, D., de Cordova, F. M., da Cunha, R. M. S., Walz, R., & Leal, R. B. (2013) · Experimental Brain Research · doi:10.1007/s00221-013-3421-8 · Cited by 78 · see citing works
Shen, Y., Tian, M., Zheng, Y., Gong, F., Fu, A. K. Y., & Ip, N. Y. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.043 · Cited by 67 · see citing works
Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action
Du, J., Machado-Vieira, R., Maeng, S., Martinowich, K., Manji, H. K., & Zarate, C. A. (2006) · Drug Discovery Today: Therapeutic Strategies · doi:10.1016/j.ddstr.2006.11.012 · Cited by 64 · see citing works
Delgado, J. Y., Coba, M., Anderson, C. N. G., Thompson, K. R., Gray, E. E., Heusner, C. L., Martin, K. C., Grant, S. G. N., & O'Dell, T. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3056-07.2007 · Cited by 62 · see citing works
Differential regulation of GluA1 expression by ketamine and memantine
Zhang, K., Yamaki, V. N., Wei, Z., Zheng, Y., & Cai, X. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.09.002 · Cited by 51 · see citing works
Ketamine’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
Yi, E.-S., Oh, S., Lee, J.-K., & Leem, Y.-H. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.03.093 · Cited by 45 · see citing works
Regulation of glutamate receptors by striatal‐enriched tyrosine phosphatase 61 (STEP<sub>61</sub>)
Won, S., & Roche, K. W. (2021) · The Journal of Physiology · doi:10.1113/jp278703 · Cited by 34 · see citing works
Allison, C., & Pratt, J. A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300800 · Cited by 27 · see citing works
Novel blockade of protein kinase A-mediated phosphorylation of AMPA receptors
Vanhoose, A. M., Clements, J. M., & Winder, D. G. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3572-05.2006 · Cited by 21 · see citing works
Lilly, S. M., Zeng, X. J., & Tietz, E. I. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01746.x · Cited by 21 · see citing works
Molecular organization and assembly of the postsynaptic density of excitatory brain synapses.
Kim, E., & Ko, J. (2006) · Results and Problems in Cell Differentiation · doi:10.1007/400_011 · Cited by 11 · see citing works
- Authors
- Banke, T. G., Bowie, D., Lee, H.-K., Huganir, R. L., Schousboe, A., & Traynelis, S. F.
- Affiliations
- University of Copenhagen (DK)
- Emory University (US)
- Howard Hughes Medical Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-01-01
- Volume
- 20
- Issue
- 1
- Pages
- 89-102
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6774102
- OpenAlex
- W2170532212
- Cited by
- 652
- References
- 3
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 15 · 2023: 12 · 2022: 15 · 2021: 17 · 2020: 20 · 2019: 18 · 2018: 33 · 2017: 30 · 2016: 27 · 2015: 27 · 2014: 30 · 2013: 22 · 2012: 20
- FWCI
- 11.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Sundhed og Sygdom, Det Frie Forskningsråd
- Medical Research Council
- 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 › Ion channel regulation and function
- Keywords
- protein kinase A, calcineurin, receptor phosphorylation, single-channel properties, synaptic plasticity, excitatory synapses
- MeSH terms
- Animals, Cells, Cultured, Hippocampus, Humans, Kidney, Membrane Potentials, Recombinant Proteins, Synapses, Transfection, Ion Channel Gating, Mutagenesis, Site-Directed, Cyclic AMP-Dependent Protein Kinases, Pyramidal Cells, Receptors, AMPA, Patch-Clamp Techniques, Glutamic Acid, Calcineurin, Rats
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