The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
Open accessAbstract
Silent synapses, or excitatory synapses that lack functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), are thought to be critical for regulation of neuronal circuits and synaptic plasticity. Here, we report that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse number, and excitatory synaptic transmission in hippocampal and cortical cultured neurons. Overexpression of SynGAP in neurons results in a remarkable depression of AMPAR-mediated miniature excitatory postsynaptic currents, a significant reduction in synaptic AMPAR surface expression, and a decrease in the insertion of AMPARs into the plasma membrane. This change is specific for AMPARs because no change is observed in synaptic NMDA receptor expression or total synapse density. In contrast to these results, synaptic transmission is increased in neurons from SynGAP knockout mice as well as in neuronal cultures treated with SynGAP small interfering RNA. In addition, activation of the extracellular signal-regulated kinase, ERK, is significantly decreased in SynGAP-overexpressing neurons, whereas P38 mitogen-activated protein kinase (MAPK) signaling is potentiated. Furthermore, ERK activation is up-regulated in neurons from SynGAP knockout mice, whereas P38 MAPK function is depressed. Taken together, these data suggest that SynGAP plays a critical role in the regulation of neuronal MAPK signaling, AMPAR membrane trafficking, and excitatory synaptic transmission.
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In the citing paper
“Studies using in vitro systems and KO mice have shown that SynGAP expression is inversely correlated to the levels of AMPA receptors, but not NMDA receptors, at the synapse [306].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [306]
In the citing paper
“In addition, disrupting SynGAP expression in dissociated hippocampal neurons can enhance dendritic spine function (Kim et al., 2005; Rumbaugh et al., 2006) or suppress it (Krapivinsky et al., 2004).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
In the citing paper
“depending on the variant expressed, SynGAP can either stimulate (Rumbaugh et al., 2006) or suppress dendritic spine synapse function (McMahon et al., 2012).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
In the citing paper
“This cassette would be expected to cause a truncation of full-length protein, which is known to inactivate SynGAP (Rumbaugh et al., 2006).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
In the citing paper
“Mechanistically, SynGAP shapes developmental synaptic function through its synaptic GAP activity, where it suppresses many biochemical signaling cascades within dendritic spines that promote growth of synapses and insertion of AMPARs (Kim et al., 2005; Krapivinsky et al., 2004; Rumbaugh et al., 2006).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
In the citing paper
“These findings are consistent with the role of SynGAP as an essential repressive factor that contributes to the developmental trajectory of glutamatergic synapse maturation (Kim et al., 2003; Rumbaugh et al., 2006; Vazquez et al., 2004).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
In the citing paper
“However, the role that SynGAP plays in neurons to regulate dendritic spine synapse function has been controversial because some studies report that SynGAP is a repressor of these synapses (Kim et al., 2005; Rumbaugh et al., 2006; Vazquez et al., 2004), while others report that it stimulates them (Krapivinsky et al., 2004; McMahon et al., 2012).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Rumbaugh et al., 2006
Citations
Cites
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
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MAPK cascade signalling and synaptic plasticity
Thomas, G. M., & Huganir, R. L. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1346 · Cited by 1,454
Self-citationRat hippocampal neurons in dispersed cell culture.
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Regulation of AMPA receptors during synaptic plasticity
Song, I., & Huganir, R. L. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02270-1 · Cited by 798
Self-citationRas and Rap control AMPA receptor trafficking during synaptic plasticity
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SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family
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Self-citationMolecular Psychology: Roles for the ERK MAP Kinase Cascade in Memory
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Self-citation
Research works printed but not linked: 1
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Cited by
Sorted by citations
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Sheng, M., & Hoogenraad, C. C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060805.160029 · Cited by 1,003
Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking
Chowdhury, S., Shepherd, J. D., Okuno, H., Lyford, G., Petralia, R. S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.033 · Cited by 792
Self-citationArc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors
Shepherd, J. D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.034 · Cited by 779
Self-citationRegulatory mechanisms of AMPA receptors in synaptic plasticity
Derkach, V. A., Oh, M. C., Guire, E. S., & Soderling, T. R. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2055 · Cited by 708
Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536
Metadata
- Authors
- Rumbaugh, G., Adams, J. P., Kim, J. H., & Huganir, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- National Institutes of Health (US)
- Department of Developmental Biology, The Rockefeller University, New York, NY 10021
- Corresponding author
- Huganir, Richard L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-03-14
- Volume
- 103
- Issue
- 12
- Pages
- 4344-4351
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1450173
- OpenAlex
- W2046170065
- Cited by
- 260
- References
- 40
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 21 · 2023: 13 · 2022: 10 · 2021: 7 · 2020: 23 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 12 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH064856)
- National Institute of Neurological Disorders and Stroke (F32NS043071)
- 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, silent synapses, AMPA receptor trafficking, excitatory synaptic transmission, Ras GTPase-activating protein, ERK signaling, p38 MAPK, synaptic plasticity, miniature excitatory postsynaptic currents, hippocampal neurons, cortical neurons
- MeSH terms
- Animals, Cells, Cultured, Mutation, Synaptic Transmission, Neurons, Synapses, Receptors, AMPA, Mice, Knockout, ras GTPase-Activating Proteins, Mitogen-Activated Protein Kinases, Protein Transport, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, Mice, Rats
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