Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
Open accessAbstract
Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for synaptic plasticity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Results based on single spine stimulations contrast earlier biochemical studies that reported persistent phosphorylation of CaMKII upon more global induction of LTP.
“It should be noted that these results based on single spine stimulations contrast earlier biochemical studies that reported persistent phosphorylation of CaMKII upon more global induction of LTP (Fukunaga et al., 1995; Barria et al., 1997; Lisman and Zhabotinsky, 2001).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Barria et al., 1997
Cites
Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons
Frey, U., Huang, Y.-Y., & Kandel, E. R. (1993) · Science · doi:10.1126/science.8389057 · Cited by 1,218 · 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
Pettit, D. L., Perlman, S., & Malinow, R. (1994) · Science · doi:10.1126/science.7997883 · Cited by 329 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Activity-dependent scaling of quantal amplitude in neocortical neurons
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C., & Nelson, S. B. (1998) · Nature · doi:10.1038/36103 · Cited by 2,226 · 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
The induction of pain: an integrative review
Millan, M. J. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00048-3 · Cited by 1,774 · see citing works
Control of memory formation through regulated expression of a CaMKII transgene
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996) · Science · doi:10.1126/science.274.5293.1678 · Cited by 1,550 · see citing works
Mechanisms 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
Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons
Ungless, M. A., Whistler, J. L., Malenka, R. C., & Bonci, A. (2001) · Nature · doi:10.1038/35079077 · Cited by 1,106 · see citing works
Shi, S.-H., Hayashi, Y., Esteban, J. A., & Malinow, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00321-x · Cited by 1,094 · see citing works
The MAPK cascade is required for mammalian associative learning
Atkins, C. M., Selcher, J. C., Petraitis, J. J., Trzaskos, J. M., & Sweatt, J. D. (1998) · Nature Neuroscience · doi:10.1038/2836 · Cited by 1,083 · see citing works
TrkB signalling pathways in LTP and learning
Minichiello, L. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2738 · Cited by 1,055 · 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
Jiang, Y.-H., Armstrong, D., Albrecht, U., Atkins, C. M., Noebels, J. L., Eichele, G., Sweatt, J. D., & Beaudet, A. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80596-6 · Cited by 852 · 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
Regulatory 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
Self-citationStructure–function of the multifunctional Ca2+/calmodulin-dependent protein kinase II
HUDMON, A., & SCHULMAN, H. (2002) · Biochemical Journal · doi:10.1042/bj20020228 · Cited by 615 · see citing works
Ehrlich, I., & Malinow, R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4733-03.2004 · Cited by 567 · see citing works
Petralia, R. S., Esteban, J. A., Wang, Y. –., Partridge, J. G., Zhao, H. –., Wenthold, R. J., & Malinow, R. (1999) · Nature Neuroscience · doi:10.1038/4532 · Cited by 496 · 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
Molecular mechanisms underlying emotional learning and memory in the lateral amygdala
Rodrigues, S. M., Schafe, G. E., & LeDoux, J. E. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.014 · Cited by 491 · see citing works
Izquierdo, I., Furini, C. R. G., & Myskiw, J. C. (2016) · Physiological Reviews · doi:10.1152/physrev.00018.2015 · Cited by 453 · see citing works
A role for synaptic plasticity in the adolescent development of executive function
Selemon, L. D. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.7 · Cited by 439 · see citing works
Shen, K., Teruel, M. N., Subramanian, K., & Meyer, T. (1998) · Neuron · doi:10.1016/s0896-6273(00)80569-3 · Cited by 350 · see citing works
Okamoto, K.-I., Narayanan, R., Lee, S. H., Murata, K., & Hayashi, Y. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701656104 · Cited by 328 · 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
Inhibitory Autophosphorylation of CaMKII Controls PSD Association, Plasticity, and Learning
Elgersma, Y., Fedorov, N. B., Ikonen, S., Choi, E. S., Elgersma, M., Carvalho, O. M., Giese, K. P., & Silva, A. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)01007-3 · Cited by 290 · see citing works
Sutton, M. A., Taylor, A. M., Ito, H. T., Pham, A., & Schuman, E. M. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.030 · Cited by 274 · 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
Bidirectional synaptic plasticity: from theory to reality
Bear, M. F. (2003) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2002.1255 · Cited by 260 · see citing works
Otmakhov, N., Tao-Cheng, J.-H., Carpenter, S., Asrican, B., Dosemeci, A., Reese, T. S., & Lisman, J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2350-04.2004 · Cited by 258 · see citing works
Long-term potentiation: outstanding questions and attempted synthesis
Lisman, J. (2003) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.2002.1242 · Cited by 240 · see citing works
A role for AMPA receptors in mood disorders
Alt, A., Nisenbaum, E. S., Bleakman, D., & Witkin, J. M. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.12.022 · Cited by 238 · see citing works
Bolton, M. M., Pittman, A. J., & Lo, D. C. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03221.2000 · Cited by 201 · see citing works
Miller, P., Zhabotinsky, A. M., Lisman, J. E., & Wang, X.-J. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030107 · Cited by 199 · see citing works
The absence of a major Ca <sup>2+</sup> signaling pathway in GABAergic neurons of the hippocampus
Sík, A., Hájos, N., Gulácsi, A., Mody, I., & Freund, T. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3245 · Cited by 186 · see citing works
Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus
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
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
Gomez, L. L., Alam, S., Smith, K. E., Horne, E., & Dell'Acqua, M. L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-16-07027.2002 · Cited by 170 · see citing works
Chang, J.-Y., Parra-Bueno, P., Laviv, T., Szatmari, E. M., Lee, S.-J. R., & Yasuda, R. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.041 · Cited by 161 · 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
Learning mechanisms: the case for CaM-KII
Lisman, J., Malenka, R. C., Nicoll, R. A., & Malinow, R. (1997) · Science · doi:10.1126/science.276.5321.2001 · Cited by 147 · see citing works
Hippocampal dopamine/DRD1 signaling dependent on the ghrelin receptor
Kern, A., Mavrikaki, M., Ullrich, C., Albarran-Zeckler, R., Brantley, A. F., & Smith, R. G. (2015) · Cell · doi:10.1016/j.cell.2015.10.062 · Cited by 136 · see citing works
Huang, C.-C., Liang, Y.-C., & Hsu, K.-S. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-22-09728.1999 · Cited by 127 · see citing works
Is Persistent Activity of Calcium/Calmodulin-Dependent Kinase Required for the Maintenance of LTP?
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
Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Saneyoshi, T., Matsuno, H., Suzuki, A., Murakoshi, H., Hedrick, N. G., Agnello, E., O’Connell, R., Stratton, M. M., Yasuda, R., & Hayashi, Y. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.012 · Cited by 119 · see citing works
αCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory
Irvine, E. E., Vernon, J., & Giese, K. P. (2005) · Nature Neuroscience · doi:10.1038/nn1431 · Cited by 119 · see citing works
Glutamatergic synapses onto hippocampal interneurons: precision timing without lasting plasticity
McBain, C. J., Freund, T. F., & Mody, I. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01347-2 · Cited by 113 · see citing works
Spaethling, J. M., Klein, D. M., Singh, P., & Meaney, D. F. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2008.0532 · Cited by 112 · 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
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
Lynch, G., Kramár, E. A., Babayan, A. H., Rumbaugh, G., & Gall, C. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.006 · Cited by 97 · see citing works
DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific
Goodell, D. J., Zaegel, V., Coultrap, S. J., Hell, J. W., & Bayer, K. U. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.068 · Cited by 88 · see citing works
CA1 Long-Term Potentiation Is Diminished but Present in Hippocampal Slices from α-CaMKII Mutant Mice
Hinds, H. L., Tonegawa, S., & Malinow, R. (1998) · Learning & Memory · doi:10.1101/lm.5.4.344 · Cited by 86 · see citing works
Cooke, S. F., Wu, J., Plattner, F., Errington, M., Rowan, M., Peters, M., Hirano, A., Bradshaw, K. D., Anwyl, R., Bliss, T. V. P., et al. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.111559 · Cited by 77 · see citing works
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
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
Barriers in the brain: resolving dendritic spine morphology and compartmentalization
Adrian, M., Kusters, R., Wierenga, C. J., Storm, C., Hoogenraad, C. C., & Kapitein, L. C. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00142 · Cited by 62 · see citing works
“It should be noted that these results based on single spine stimulations contrast earlier biochemical studies that reported persistent phosphorylation of CaMKII upon more global induction of LTP (Fukunaga et al., 1995; Barria et al., 1997; Lisman and Zhabotinsky, 2001).”
InfluentialDelgado, 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
Homeostatic regulation of glutamatergic transmission by dopamine D <sub>4</sub> receptors
Yuen, E. Y., Zhong, P., & Yan, Z. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010025108 · Cited by 54 · see citing works
Plasticity in the Hippocampus, Neurogenesis and Drugs of Abuse
Avchalumov, Y., & Mandyam, C. D. (2021) · Brain Sciences · doi:10.3390/brainsci11030404 · Cited by 49 · see citing works
Cognitive Remediation in Schizophrenia
Kaneko, Y., & Keshavan, M. (2012) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2012.10.3.125 · Cited by 51 · see citing works
Targeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · 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
Subcellular organization of camkii in rat hippocampal pyramidal neurons
Ding, J., Kennedy, M. B., & Weinberg, R. J. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23372 · Cited by 45 · see citing works
Spaethling, J., Le, L., & Meaney, D. F. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.03.003 · Cited by 36 · 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
Blackwell, K. T., & Jedrzejewska‐Szmek, J. (2013) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1240 · Cited by 17 · see citing works
- Authors
- Barria, A., Muller, D., Derkach, V., Griffith, L. C., & Soderling, T. R.
- Affiliations
- A. Barria, V. Derkach, T. R. Soderling, Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA.
- University of Geneva (CH)
- Corresponding author
- Soderling, Thomas R.
- ORCID
- Griffith, Leslie C.
- Venue
- Science
- Published
- 1997-06-27
- Volume
- 276
- Issue
- 5321
- Pages
- 2042-2045
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2052322593
- Cited by
- 1,049
- References
- 3
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 19 · 2023: 16 · 2022: 21 · 2021: 20 · 2020: 23 · 2019: 26 · 2018: 24 · 2017: 32 · 2016: 24 · 2015: 23 · 2014: 42 · 2013: 36 · 2012: 53
- FWCI
- 23.50
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (R01GM054408)
- National Institute of Neurological Disorders and Stroke (R01NS027037, NS 27037)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPA receptors, calcium/calmodulin-dependent protein kinase II, long-term potentiation, receptor phosphorylation, GluR1, autophosphorylation, KN-62, synaptic plasticity, postsynaptic mechanisms, learning and memory, excitatory synaptic transmission
- MeSH terms
- Animals, Calcium, Cell Line, Enzyme Inhibitors, Hippocampus, Humans, Male, Synaptic Transmission, Peptide Mapping, Phosphorylation, 2-Amino-5-phosphonovalerate, Rats, Sprague-Dawley, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Excitatory Amino Acid Antagonists, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review