Autophosphorylation at Thr 286 of the α Calcium-Calmodulin Kinase II in LTP and Learning
Abstract
The calcium-calmodulin-dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the alphaCaMKII gene that blocked the autophosphorylation of threonine at position 286 (Thr286) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N-methyl-D-aspartate receptor-dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of alphaCaMKII at Thr286 appears to be required for LTP and learning.
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NMDAR-dependent LTP has been most tightly associated with intact animal behavioral memory.
“Additionally, NMDAR-dependent LTP has been most tightly associated with intact animal behavioral memory (19, 43–46).”
From Synaptic memory and CaMKII (2023) · cites this paper as [43]
Most genetic deletion studies have failed to observe effects on baseline synaptic transmission.
“However, as mentioned above, most genetic deletion studies have failed to observe effects on baseline synaptic transmission (Refs. 43, 204, 205, but see Ref. 206).”
From Synaptic memory and CaMKII (2023) · cites this paper as [43]
NMDAR-dependent LTP is greatly impaired when T286 is replaced by T286A.
“Foremost are data, now long accepted, that NMDAR-dependent LTP is greatly impaired when T286 is replaced by T286A (43, 121, 381–384).”
From Synaptic memory and CaMKII (2023) · cites this paper as [43]
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- Authors
- Giese, K. P., Fedorov, N. B., Filipkowski, R. K., & Silva, A. J.
- Affiliations
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Corresponding author
- Silva, Alcino J.
- Venue
- Science
- Published
- 1998-02-06
- Volume
- 279
- Issue
- 5352
- Pages
- 870-873
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2106389606
- Cited by
- 1,055
- References
- 2
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 27 · 2023: 34 · 2022: 33 · 2021: 36 · 2020: 38 · 2019: 35 · 2018: 31 · 2017: 48 · 2016: 27 · 2015: 50 · 2014: 49 · 2013: 47 · 2012: 47
- FWCI
- 14.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute on Aging (AG 13622)
- 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
- CaMKII, CaMKIIα, autophosphorylation, long-term potentiation, spatial learning, hippocampus, NMDA receptor, mouse mutants, CA1
- MeSH terms
- Animals, Calmodulin, Hippocampus, Mice, Inbred C57BL, Mice, Mutant Strains, Synaptic Transmission, Phosphorylation, Phosphothreonine, Picrotoxin, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Point Mutation, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Pyramidal Cells, Gene Targeting, Patch-Clamp Techniques, 6-Cyano-7-nitroquinoxaline-2,3-dione, Maze Learning, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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