Destabilization of the Postsynaptic Density by PSD-95 Serine 73 Phosphorylation Inhibits Spine Growth and Synaptic Plasticity
Open accessAbstract
Long-term potentiation (LTP) is accompanied by dendritic spine growth and changes in the composition of the postsynaptic density (PSD). We find that activity-dependent growth of apical spines of CA1 pyramidal neurons is accompanied by destabilization of the PSD that results in transient loss and rapid replacement of PSD-95 and SHANK2. Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multiple signals to regulate morphological plasticity. Activity-dependent trafficking of PSD-95 is triggered by phosphorylation at serine 73, a conserved calcium/calmodulin-dependent protein kinase II (CaMKII) consensus phosphorylation site, which negatively regulates spine growth and potentiation of synaptic currents. We propose that PSD-95 and CaMKII act at multiple steps during plasticity induction to initially trigger and later terminate spine growth by trafficking growth-promoting PSD proteins out of the active spine.
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Expression of the phosphomimic mutation S73D prevents LTP expression.
“Surprisingly, expression of a phosphomimic mutation, S73D, prevents LTP expression (296).”
From Synaptic memory and CaMKII (2023) · cites this paper as [296]
Shank2 is implicated in activity-dependent spine remodeling.
“whereas Shank2 has been implicated in activity-dependent spine remodeling34.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [34]
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- Authors
- Steiner, P., Higley, M. J., Xu, W., Czervionke, B. L., Malenka, R. C., & Sabatini, B. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Stanford Medicine (US)
- Corresponding author
- Sabatini, Bernardo L.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 60
- Issue
- 5
- Pages
- 788-802
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2671083
- OpenAlex
- W2065359670
- Cited by
- 259
- References
- 73
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- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-01-15)
- Open access
- bronze
- doi.org
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- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1725 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (113192)
- National Institutes of Health (5r01ns005270-23)
- National Institute of Mental Health (MH 063394, R37MH063394, R01MH063394, R00MH080310, K99MH080310, MH080310)
- National Institute of Neurological Disorders and Stroke (NS-05270, R01NS052707)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- postsynaptic density, PSD-95, CaMKII, synaptic plasticity, long-term potentiation, Shank2, protein trafficking, CA1 pyramidal neurons, morphological plasticity, PDZ domain, guanylate kinase domain, calcium/calmodulin-dependent protein kinase
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Animals, Newborn, Electric Stimulation, Enzyme Inhibitors, Glutamates, Hippocampus, Indoles, Membrane Proteins, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Organ Culture Techniques, Phosphorylation, Piperazines, Serine, Time Factors, Rats, Sprague-Dawley, Point Mutation, Protein Structure, Tertiary, Long-Term Potentiation, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Protein Transport, Intracellular Signaling Peptides and Proteins, Dendritic Spines, Green Fluorescent Proteins, Rats
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 ›
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