Phosphorylation of the α-Amino-3-hydroxy-5-methylisoxazole4-propionic Acid Receptor GluR1 Subunit by Calcium/ Calmodulin-dependent Kinase II
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Modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid (AMPA) receptors in the brain by protein phosphorylation may play a crucial role in the regulation of synaptic plasticity. Previous studies have demonstrated that calmodulin (CaM) kinase II can phosphorylate and modulate AMPA receptors. However, the sites of CaM kinase phosphorylation have not been unequivocally identified. In the current study, we have generated two phosphorylation site-specific antibodies to analyze the phosphorylation of the glutamate receptor GluR1 subunit. These antibodies recognize GluR1 only when it is phosphorylated on serine residues 831 or 845. We have used these antibodies to demonstrate that serine 831 is specifically phosphorylated by CaM kinase II in transfected cells expressing GluR1 as well as in hippocampal slice preparations. Two-dimensional phosphopeptide mapping experiments indicate that Ser-831 is the major site of CaM kinase II phosphorylation on GluR1. In addition, treatment of hippocampal slice preparations with phorbol esters and forskolin increase the phosphorylation of serine 831 and 845, respectively, indicating that protein kinase C and protein kinase A phosphorylate these residues in hippocampal slices. These results identify the site of CaM kinase phosphorylation of the GluR1 subunit and demonstrate that GluR1 is multiply phosphorylated by protein kinase A, protein kinase C, and CaM kinase II in situ.
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NMDAR-dependent LTP requires Ca2+ influx leading to activation of CaMKII/PKC which directly phosphorylate GluA1 S831, increasing GluA1 single channel conductance and promoting GluA1 targeting to the PSD.
“NMDAR-dependent LTP requires Ca2+ influx leading to activation of CaMKII/PKC which directly phosphorylate GluA1 S831, increasing GluA1 single channel conductance and promoting GluA1 targeting to the PSD (Mammen et al., 1997, Barria et al., 1997a, Derkach et al., 1999, Kristensen et al., 2011, Barria et al., 1997b).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Mammen et al., 1997
Cites
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
Manabe, T., Renner, P., & Nicoll, R. A. (1992) · Nature · doi:10.1038/355050a0 · Cited by 366 · see citing works
Pettit, D. L., Perlman, S., & Malinow, R. (1994) · Science · doi:10.1126/science.7997883 · Cited by 329 · see citing works
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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
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
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588 · see citing works
The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860 · see citing works
AMPARs and Synaptic Plasticity: The Last 25 Years
Huganir, R. L., & Nicoll, R. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.025 · Cited by 968 · see citing works
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Diering, G. H., & Huganir, R. L. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.018 · Cited by 844 · see citing works
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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-citationMolecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment
Konradi, C., & Heckers, S. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00328-5 · Cited by 336 · see citing works
Pathways of the Past: the Imprint of Memory
Horn, G. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1324 · Cited by 308 · see citing works
Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704391104 · Cited by 290 · see citing works
Role of the brain‐derived neurotrophic factor at glutamatergic synapses
Carvalho, A. L., Caldeira, M. V., Santos, S. D., & Duarte, C. B. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707509 · Cited by 290 · see citing works
Lee, H.-K., Takamiya, K., He, K., Song, L., & Huganir, R. L. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00835.2009 · Cited by 261 · see citing works
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Abel, T., & Nguyen, P. V. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(07)00006-4 · Cited by 198 · see citing works
Poncer, J. C., Esteban, J. A., & Malinow, R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-11-04406.2002 · Cited by 177 · see citing works
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Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
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Chen, H.-X., Otmakhov, N., Strack, S., Colbran, R. J., & Lisman, J. E. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.85.4.1368 · Cited by 126 · see citing works
Selvakumar, B., Jenkins, M. A., Hussain, N. K., Huganir, R. L., Traynelis, S. F., & Snyder, S. H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221295110 · Cited by 97 · see citing works
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Guntupalli, S., Jang, S. E., Zhu, T., Huganir, R. L., Widagdo, J., & Anggono, V. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.774554 · Cited by 70 · see citing works
Self-citationDelgado, 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
Klug, J. R., Mathur, B. N., Kash, T. L., Wang, H.-D., Matthews, R. T., Robison, A. J., Anderson, M. E., Deutch, A. Y., Lovinger, D. M., Colbran, R. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045323 · Cited by 49 · see citing works
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Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · see citing works
Gu, Z., Jiang, Q., Yuen, E. Y., & Yan, Z. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.018853 · Cited by 35 · see citing works
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Won, S., & Roche, K. W. (2021) · The Journal of Physiology · doi:10.1113/jp278703 · Cited by 34 · see citing works
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Higa, G. S. V., Viana, F. J. C., Francis-Oliveira, J., Cruvinel, E., Franchin, T. S., Marcourakis, T., Ulrich, H., & De Pasquale, R. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110036 · Cited by 29 · see citing works
Andreetta, F., Carboni, L., Grafton, G., Jeggo, R., Whyment, A. D., van den Top, M., Hoyer, D., Spanswick, D., & Barnes, N. M. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13432 · Cited by 28 · 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
- Authors
- Mammen, A. L., Kameyama, K., Roche, K. W., & Huganir, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Huganir, Richard L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 272
- Issue
- 51
- Pages
- 32528-32533
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1978155331
- Cited by
- 441
- References
- 3
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 12 · 2023: 7 · 2022: 5 · 2021: 15 · 2020: 10 · 2019: 7 · 2018: 15 · 2017: 16 · 2016: 14 · 2015: 14 · 2014: 21 · 2013: 19 · 2012: 20
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- AMPA receptors, GluR1 subunit, calcium/calmodulin-dependent protein kinase II, protein phosphorylation, protein kinase A, protein kinase C, phorbol ester, forskolin, hippocampus, synaptic plasticity
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Male, Peptide Mapping, Phosphopeptides, Phosphorylation, Rats, Sprague-Dawley, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
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