SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family

Kim, Jee Hae; Liao, Dezhi; Lau, Lit-Fui; Huganir, Richard L

doi:10.1016/s0896-6273(00)81008-9

Cited by 634Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingGenetics and Neurodevelopmental Disorders

SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family

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Kim, Jee Hae, Liao, Dezhi, Lau, Lit-Fui, Huganir, Richard L·1998·Neuron

DOI 10.1016/s0896-6273(00)81008-9

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Abstract

The PSD-95/SAP90 family of proteins has recently been implicated in the organization of synaptic structure. Here, we describe the isolation of a novel Ras-GTPase activating protein, SynGAP, that interacts with the PDZ domains of PSD-95 and SAP102 in vitro and in vivo. SynGAP is selectively expressed in brain and is highly enriched at excitatory synapses, where it is present in a large macromolecular complex with PSD-95 and the NMDA receptor. SynGAP stimulates the GTPase activity of Ras, suggesting that it negatively regulates Ras activity at excitatory synapses. Ras signaling at the postsynaptic membrane may be involved in the modulation of excitatory synaptic transmission by NMDA receptors and neurotrophins. These results indicate that SynGAP may play an important role in the modulation of synaptic plasticity.

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SynGAP1 is a Ras-GTPase activating protein located in the postsynaptic density of glutamatergic neurons and participates in dendritic spine maturation, glutamate receptor trafficking, and synaptic function.
“Synaptic GTPase activating protein 1 (SynGAP1) is a Ras-GTPase activating protein localized in the PSD in glutamatergic neurons [66, 197] and involved in dendritic spine maturation, glutamate receptor trafficking and synaptic function [11].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [197]
SYNGAP1 encodes a synaptic RasGAP (SynGAP) largely localized to dendritic spines in neocortical pyramidal neurons, where it suppresses signaling linked to NMDAR-mediated plasticity and AMPAR membrane insertion.
“SYNGAP1 encodes a synaptic RasGAP (SynGAP) that is largely localized to dendritic spines in neocortical pyramidal neurons (Chen et al., 1998; Kim et al., 1998; Zhang et al., 1999), where it suppresses signaling pathways linked to NMDA receptor (NMDAR) mediated synaptic plasticity and AMPA receptor (AMPAR) membrane insertion”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Kim et al., 1998
The GABAergic elevation is likely explained by homeostatic upregulation caused by elevated network excitation triggered by prematurely developing spine synapses.
“However, because SynGAP is selectively localized to excitatory synapses (Chen et al., 1998; Kim et al., 1998), this effect is likely explained by a homoeostatic upregulation of the GABAergic system caused by elevated network excitation triggered by prematurely developing spine synapses.”
From Pathogenic SYNGAP1 Mutations Impair Cognitive Development by Disrupting Maturation of Dendritic Spine Synapses (2012) · cites this paper as Kim et al., 1998

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Authors: Kim, J. H., Liao, D., Lau, L.-F., & Huganir, R. L.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Huganir, Richard L
ORCID: Liao, Dezhi
Huganir, Richard L
Venue: Neuron
Publisher: Elsevier BV
Published: 1998-04
Volume: 20
Issue: 4
Pages: 683-691
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(00)81008-9
OpenAlex: W2027230597
Cited by: 634
References: 70
Citations by year: 2026: 11 · 2025: 23 · 2024: 23 · 2023: 18 · 2022: 19 · 2021: 18 · 2020: 24 · 2019: 16 · 2018: 19 · 2017: 16 · 2016: 15 · 2015: 9 · 2014: 16 · 2013: 13 · 2012: 15
FWCI: 18.85
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 1106 d)
Locations: Neuron (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: National Institutes of Health (5t32ns007368-10)
National Institute of Neurological Disorders and Stroke (T32NS07368)
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, PSD-95, SAP102, PDZ domain, synaptic organization, excitatory synapses, NMDA receptor, Ras signaling, synaptic plasticity, neurotrophins, postsynaptic membrane
MeSH terms: SAP90-PSD95 Associated Proteins, Disks Large Homolog 4 Protein, Amino Acid Sequence, Animals, Brain, Carrier Proteins, Cell Line, Cells, Cultured, Cloning, Molecular, Hippocampus, Humans, Male, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Organ Specificity, Proteins, Saccharomyces cerevisiae, Synapses, Transfection, Sequence Alignment, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, GTPase-Activating Proteins, ras GTPase-Activating Proteins, Intracellular Signaling Peptides and Proteins, Rats

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SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family

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