Mass of the postsynaptic density and enumeration of three key molecules
Open accessAbstract
The total molecular mass of individual postsynaptic densities (PSDs) isolated from rat forebrain was measured by scanning transmission EM. PSDs had a mean diameter of 360 nm and molecular mass of 1.10 +/- 0.36 GDa. Because the mass represents the sum of the molecular masses of all of the molecules comprising a PSD, it becomes possible to derive the number of copies of each protein, once its relative mass contribution is known. Mass contributions of PSD-95, synapse-associated protein (SAP)97, and alpha-Ca2+/calmodulin-dependent protein kinase II (CaMKII) were determined by quantitative gel electrophoresis of PSD fractions. The number of PSD-95 molecules per average PSD, contributing 2.3% of the mass of the PSD, was calculated to be 300, whereas the number of SAP97 molecules, contributing 0.9% of the mass of the PSD, was 90. The alpha-CaMKII holoenzymes, which contribute 6% of the mass when brains are homogenized within 2 min of interrupting blood flow, have 80 holoenzymes associated with a typical PSD. When blood flow is interrupted 15 min before homogenization, the average mass of PSDs increases by approximately 40%. The additional alpha-CaMKII associated with PSDs accounts for up to 20% of this mass increase, representing the addition of 100-200 alpha-CaMKII holoenzymes.
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CaMKII is present in the brain at extraordinarily high levels, rivaling the levels of cytoskeletal proteins.
“Second, it is present in the brain at extraordinarily high levels, rivaling the levels of cytoskeletal proteins (63–67), suggesting that CaMKII may play a structural role (27, 68).”
From Synaptic memory and CaMKII (2023) · cites this paper as [65]
Given roughly 20-30 NMDARs in the PSD and ∼100 holoenzymes (∼1,200 CaMKII subunits), after NMDAR activation only a small fraction of subunits per holoenzyme would be directly bound to GluN2B.
“since there are roughly 20–30 NMDARs in the PSD (66, 143) and ∼100 holoenzymes [∼1,200 CaMKII subunits (65)], after NMDAR activation only a small fraction of subunits per holoenzyme would be directly bound to GluN2B.”
From Synaptic memory and CaMKII (2023) · cites this paper as [65]
On average there are approximately 250 PSD-95 molecules in the PSD and approximately 50 AMPARs, although this number is highly variable.
“On average there are ∼250 PSD-95 molecules in the PSD (65) and, on average, ∼50 AMPARs, although this number is highly variable (143, 290, 291).”
From Synaptic memory and CaMKII (2023) · cites this paper as [65]
The number of PSD-95 molecules is roughly 200-300, and the number of CaMKII holoenzymes is estimated to be roughly 80.
“The number of PSD-95 molecules is roughly 200–300 (65), and the number of CaMKII holoenzymes is estimated to be roughly 80 (65).”
From Synaptic memory and CaMKII (2023) · cites this paper as [65]
The number of CaMKII molecules bound to the PSD in a fully activated synapse is estimated to be 270.
“The number of CaMKII molecules bound to the PSD in a fully activated synapse is estimated to be 270 (65).”
From Synaptic memory and CaMKII (2023) · cites this paper as [65]
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“It is composed of mainly the α and β isoforms, is enriched in the PSD, and is one of the most abundant proteins in the brain (Chen et al., 2005).”
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- Authors
- Chen, X., Vinade, L., Leapman, R. D., Petersen, J. D., Nakagawa, T., Phillips, T. M., Sheng, M., & Reese, T. S.
- Affiliations
- National Institutes of Health (US)
- Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive, MSC 4062, Bethesda, MD 20892; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul/Foundation of Support to the Research of the State of the Rio Grande do Sul, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil; Division of Bioengineering and Physical Science, Office of Research Services, Office of the Director, National Institutes of Health, 9000...
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-08
- Volume
- 102
- Issue
- 32
- Pages
- 11551-11556
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1182136
- OpenAlex
- W2094011563
- Cited by
- 236
- References
- 6
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 5 · 2020: 7 · 2019: 14 · 2018: 17 · 2017: 12 · 2016: 14 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 13
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- postsynaptic density, molecular weight, PSD-95, SAP97, CaMKII, synaptic proteins, protein copy number
- MeSH terms
- Animals, Electrophoresis, Membrane Proteins, Microscopy, Electron, Nerve Tissue Proteins, Prosencephalon, Calcium-Calmodulin-Dependent Protein Kinases, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Rats
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