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Citron Binds to PSD-95 at Glutamatergic Synapses on Inhibitory Neurons in the Hippocampus
Open accessAbstract
Synaptic NMDA-type glutamate receptors are anchored to the second of three PDZ (PSD-95/Discs large/ZO-1) domains in the postsynaptic density (PSD) protein PSD-95. Here, we report that citron, a protein target for the activated form of the small GTP-binding protein Rho, preferentially binds the third PDZ domain of PSD-95. In GABAergic neurons from the hippocampus, citron forms a complex with PSD-95 and is concentrated at the postsynaptic side of glutamatergic synapses. Citron is expressed only at low levels in glutamatergic neurons in the hippocampus and is not detectable at synapses onto these neurons. In contrast to citron, p135 SynGAP, an abundant synaptic Ras GTPase-activating protein that can bind to all three PDZ domains of PSD-95, and Ca 2+/calmodulin-dependent protein kinase II (CaM kinase II) are concentrated postsynaptically at glutamatergic synapses on glutamatergic neurons. CaM kinase II is not expressed and p135 SynGAP is expressed in less than half of hippocampal GABAergic neurons. Segregation of citron into inhibitory neurons does not occur in other brain regions. For example, citron is expressed at high levels in most thalamic neurons, which are primarily glutamatergic and contain CaM kinase II. In several other brain regions, citron is present in a subset of neurons that can be either GABAergic or glutamatergic and can sometimes express CaM kinase II. Thus, in the hippocampus, signal transduction complexes associated with postsynaptic NMDA receptors are different in glutamatergic and GABAergic neurons and are specialized in a way that is specific to the hippocampus.
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“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 Zhang et al., 1999
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Metadata
- Authors
- Zhang, W., Vazquez, L., Apperson, M., & Kennedy, M. B.
- Affiliations
- California Institute of Technology (US)
- ORCID
- Kennedy, Mary B.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-01-01
- Volume
- 19
- Issue
- 1
- Pages
- 96-108
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782379
- OpenAlex
- W2111810014
- Cited by
- 190
- References
- 60
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation (9023446)
- U.S. Public Health Service
- National Institute of Neurological Disorders and Stroke (R01NS028710, NS28710)
- 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
- citron, PSD-95, PDZ domain, glutamatergic synapses, GABAergic neurons, hippocampus, Rho GTPases, SynGAP, CaM kinase II, thalamic neurons, synaptic protein localization
- MeSH terms
- Amino Acid Sequence, Brain Chemistry, Cells, Cultured, gamma-Aminobutyric Acid, Hippocampus, Molecular Sequence Data, Nerve Tissue Proteins, Neural Inhibition, Neurons, Protein Binding, Proteins, Synapses, Signal Transduction, Sequence Homology, Amino Acid, Glutamic Acid
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