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Cited by 46Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsProtein Kinase Regulation and GTPase Signaling

Quantitative estimates of the cytoplasmic, PSD, and NMDAR-bound pools of CaMKII in dendritic spines

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Feng, Bihua, Raghavachari, Sridhar, Lisman, John·2011·Brain Research
DOI 10.1016/j.brainres.2011.08.051PMC PMC3196057
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Abstract

CaMKII plays a critical role in long-term potentiation (LTP). The kinase is a major component of the postsynaptic density (PSD); however, it is also contained in the spine cytoplasm. CaMKII can now be monitored optically in living neurons, and it is therefore important to understand the contribution of the PSD and cytoplasmic pools to optical signals. Here, we estimate the size of these pools under basal conditions. From EM immunolabeling data, we calculate that the PSD/cytoplasmic ratio is ~5%. A second independent estimate is derived from measurements indicating that the average mushroom spine PSD contains 90 to 240 holoenzymes. A cytoplasmic concentration of 16 μM (~2590 holoenzymes) in the spine can be estimated from the total measured CaMKII content of hippocampal tissue, the relative volume of different compartments, and the spine-dendrite ratio of CaMKII (2:1). These numbers yield a second estimate (6%) of the PSD/spine ratio in good agreement with the first. The CaMKII bound to the NMDAR is important because preventing the formation of this complex blocks LTP induction. We estimate that the percentage of spine CaMKII held active by binding to the NMDAR is ~0.2%. Implications of the high spine concentration of CaMKII (> 100 μM alpha subunits) and the small fraction within the PSD are discussed. Of particular note, the finding that the CaMKII signal in spines shows only transient activation (open state) after LTP induction is subject to the qualification that it does not reflect the small but important pool bound to the NMDAR.

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  • Based on quantitative estimates of CaMKII distribution in spines, it was proposed that the active CaMKII bound to the NMDAR was small (∼1%).

    “Indeed, based on quantitative estimates of CaMKII distribution in spines (380), it was proposed that the active CaMKII bound to the NMDAR was small (∼1%).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [380]

    The Discussion ('Fraction of tightly bound CaMKII') estimates that about 1% of spine CaMKII is bound to NR2B under basal conditions, but distinguishes that from the fraction activated by binding, which it estimates at about 0.2%. The claim captures that the active pool is small but assigns it the percentage for the bound pool. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Feng, B., Raghavachari, S., & Lisman, J.
Affiliations
  • Brandeis University (US)
  • Duke University (US)
Corresponding author
Lisman, John
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
2011-10
Volume
1419
Pages
46-52
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/j.brainres.2011.08.051
PMC
PMC3196057
OpenAlex
W2006683312
Cited by
46
References
11
Citations by year
2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 8 · 2013: 2 · 2012: 10
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R01 NS27337, R01 DA027807)
  • Lawrence Ellison Foundation
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, dendritic spines, postsynaptic density, NMDA receptor, long-term potentiation, hippocampus
MeSH terms
Animals, Cytoplasm, Hippocampus, Receptors, N-Methyl-D-Aspartate, Dendritic Spines, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Post-Synaptic Density, Primary Cell Culture

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