Dynamic Control of CaMKII Translocation and Localization in Hippocampal Neurons by NMDA Receptor Stimulation
Abstract
Calcium-calmodulin-dependent protein kinase II (CaMKII) is thought to increase synaptic strength by phosphorylating postsynaptic density (PSD) ion channels and signaling proteins. It is shown that N-methyl-D-aspartate (NMDA) receptor stimulation reversibly translocates green fluorescent protein-tagged CaMKII from an F-actin-bound to a PSD-bound state. The translocation time was controlled by the ratio of expressed beta-CaMKII to alpha-CaMKII isoforms. Although F-actin dissociation into the cytosol required autophosphorylation of or calcium-calmodulin binding to beta-CaMKII, PSD translocation required binding of calcium-calmodulin to either the alpha- or beta-CaMKII subunits. Autophosphorylation of CaMKII indirectly prolongs its PSD localization by increasing the calmodulin-binding affinity.
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Inactive CaMKIIβ, but not α, binds with high affinity to F-actin.
“A second difference is the specific high-affinity binding of the inactive β, but not α, to F-actin (167–170).”
From Synaptic memory and CaMKII (2023) · cites this paper as [169]
Activation of CaMKII results in the rapid translocation of CaMKII to the PSD.
“activation of CaMKII results in the rapid translocation of CaMKII to the PSD (137, 140, 169, 216–220).”
From Synaptic memory and CaMKII (2023) · cites this paper as [169]
The Ca2+/CaM-dependent binding and phase separation (LLPS) of CaMKII to GluN2B can occur in the absence of enzymatic activity.
“It is well established that the Ca2+/CaM-dependent binding and phase separation (LLPS) of CaMKII to GluN2B can occur in the absence of enzymatic activity (169, 323, 376).”
From Synaptic memory and CaMKII (2023) · cites this paper as [169]
As long as Ca2+/CaM is present, binding and phase separation are maintained even with a phosphonull mutant of T286 (T286A) or with a kinase-dead mutant of CaMKII, although the binding of CaMKII to GluN2B is modestly enhanced by T286 phosphorylation.
“As long as Ca2+/CaM is present, binding and phase separation are maintained even with a phosphonull mutant of T286 (T286A) (78, 169, 323, 377) or with a kinase-dead mutant of CaMKII (169, 323, 378, 379), although the binding of CaMKII to GluN2B is modestly enhanced by T286 phosphorylation (378).”
From Synaptic memory and CaMKII (2023) · cites this paper as [169]
T286 phosphorylation is needed for the persistence of a CaMKII-GluN2B complex.
“This suggests a need for T286 phosphorylation for persistence of a CaMKII-GluN2B complex (88, 169).”
From Synaptic memory and CaMKII (2023) · cites this paper as [169]
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- Authors
- Shen, K., & Meyer, T.
- Affiliations
- Duke University (US)
- Corresponding author
- Meyer, Tobias
- Venue
- Science
- Published
- 1999-04-02
- Volume
- 284
- Issue
- 5411
- Pages
- 162-167
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2078401020
- Cited by
- 673
- References
- 2
- Citations by year
- 2026: 5 · 2025: 18 · 2024: 10 · 2023: 8 · 2022: 21 · 2021: 14 · 2020: 29 · 2019: 18 · 2018: 26 · 2017: 21 · 2016: 18 · 2015: 19 · 2014: 27 · 2013: 35 · 2012: 30
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-48113)
- 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 › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- CaMKII, postsynaptic density, subcellular translocation, hippocampal neurons, CaMKIIα, autophosphorylation, calmodulin binding, F-actin, synaptic plasticity, green fluorescent protein tagging
- MeSH terms
- Actins, Animals, Calcium, Cells, Cultured, Cytosol, Dendrites, Electric Stimulation, Hippocampus, Isoenzymes, Luminescent Proteins, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Phosphorylation, Synapses, Tumor Cells, Cultured, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Glutamic Acid, Green Fluorescent Proteins, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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