The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity
Open accessAbstract
Synaptic GTPase-activating protein (SynGAP) is a neuronal RasGAP (Ras GTPase-activating protein) that is selectively expressed in brain and highly enriched at excitatory synapses, where it negatively regulates Ras activity and its downstream signaling pathways. To investigate the physiological role of SynGAP in the brain, we have generated mutant mice lacking the SynGAP protein. These mice exhibit postnatal lethality, indicating that SynGAP plays a critical role during neuronal development. In addition, cell biological experiments show that neuronal cultures from mutant mice have more synaptic AMPA receptor clusters, suggesting that SynGAP regulates glutamate receptor synaptic targeting. Moreover, electrophysiological studies demonstrated that heterozygous mutant mice have a specific defect in hippocampal long-term potentiation (LTP). These studies show that the regulation of synaptic Ras signaling by SynGAP is important for proper neuronal development and glutamate receptor trafficking and is critical for the induction of LTP.
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Adult SynGAP heterozygous knockout mice are reported to have normal synaptic transmission and only modest defects in synaptic plasticity.
“Interestingly, adult SynGAP Heterozygous knockout mice (Hets), which model human SYNGAP1 haploinsufficiency and offer construct validity, are reported to have normal synaptic transmission and only modest defects in synaptic plasticity”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Kim et al., 2003
These findings are consistent with SynGAP acting as an essential repressive factor that contributes to the developmental trajectory of glutamatergic synapse maturation.
“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 Kim et al., 2003
The accelerated maturation hypothesis explains why others have failed to detect changes in hippocampal synaptic strength in adult SynGAP heterozygous mice.
“Our proposed “accelerated maturation” hypothesis also explains why others have failed to detect changes in hippocampal synaptic strength in adult SynGAP Het mice (Kim et al., 2003; Komiyama et al., 2002).”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Kim et al., 2003
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- Authors
- Kim, J. H., Lee, H.-K., Takamiya, K., & Huganir, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-02-15
- Volume
- 23
- Issue
- 4
- Pages
- 1119-1124
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742247
- OpenAlex
- W2108122441
- Cited by
- 240
- References
- 33
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 9 · 2020: 18 · 2019: 10 · 2018: 12 · 2017: 10 · 2016: 8 · 2015: 7 · 2014: 13 · 2013: 5 · 2012: 5
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- SynGAP, Ras GTPase-activating protein, neuronal development, synaptic plasticity, long-term potentiation, AMPA receptor trafficking, Ras signaling, excitatory synapses, postnatal lethality, hippocampus
- MeSH terms
- Animals, Brain, Cells, Cultured, Synaptic Transmission, Neuronal Plasticity, Neurons, Neuropeptides, Survival Analysis, Long-Term Potentiation, Receptors, AMPA, Mice, Knockout, Gene Targeting, GTPase-Activating Proteins, Mice
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