Camkii-Mediated Phosphorylation Regulates Distributions of Syngap-α1 and –α2 at the Postsynaptic Density
Open accessAbstract
SynGAP, a protein abundant at the postsynaptic density (PSD) of glutamatergic neurons, is known to modulate synaptic strength by regulating the incorporation of AMPA receptors at the synapse. Two isoforms of SynGAP, α1 and α2, which differ in their C-termini, have opposing effects on synaptic strength. In the present study, antibodies specific for SynGAP-α1 and SynGAP-α2 are used to compare the distribution patterns of the two isoforms at the postsynaptic density (PSD) under basal and excitatory conditions. Western immunoblotting shows enrichment of both isoforms in PSD fractions isolated from adult rat brain. Immunogold electron microscopy of rat hippocampal neuronal cultures shows similar distribution of both isoforms at the PSD, with a high density of immunolabel within the PSD core under basal conditions. Application of NMDA promotes movement of SynGAP-α1 as well as SynGAP-α2 out of the PSD core. In isolated PSDs both isoforms of SynGAP can be phosphorylated upon activation of the endogenous CaMKII. Application of tatCN21, a cell-penetrating inhibitor of CaMKII, to hippocampal neuronal cultures blocks NMDA-induced redistribution of SynGAP-α1 and SynGAP-α2. Thus CaMKII activation promotes the removal of two distinct C-terminal SynGAP variants from the PSD.
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Phosphorylation triggers movement of SynGAP out of the PSD.
“Imaging studies have reported that this phosphorylation triggers movement of SynGAP out of the PSD (304, 305)”
From Synaptic memory and CaMKII (2023) · cites this paper as [305]
The Discussion reports that NMDA stimulation moves both SynGAP isoforms out of the PSD core and that inhibiting CaMKII blocks this redistribution. The paper links the movement to CaMKII-mediated phosphorylation, but its imaging shows movement out of the PSD core, not out of the PSD complex as the claim states (Discussion; page not available). (LLM, conf=0.88)
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Self-citation
- Authors
- Yang, Y., Tao-Cheng, J.-H., Bayer, K. U., Reese, T. S., & Dosemeci, A.
- Affiliations
- National Institutes of Health (US)
- University of Colorado Anschutz (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-13
- Volume
- 8
- Issue
- 8
- Pages
- e71795
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3742523
- OpenAlex
- W2086586417
- Cited by
- 35
- References
- 30
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 3
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS081248, R01NS081248)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- SynGAP, CaMKII, protein phosphorylation, postsynaptic density, synaptic efficacy, NMDA, hippocampal neurons, glutamatergic synapses
- MeSH terms
- Animals, Calcium, Calmodulin, Enzyme Activation, Phosphorylation, Synaptic Membranes, N-Methylaspartate, GTPase-Activating Proteins, Protein Transport, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Post-Synaptic Density
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