Role of Actin in Anchoring Postsynaptic Receptors in Cultured Hippocampal Neurons: Differential Attachment of NMDA versus AMPA Receptors
Open accessAbstract
We used actin-perturbing agents and detergent extraction of primary hippocampal cultures to test directly the role of the actin cytoskeleton in localizing GABA A receptors, AMPA- and NMDA-type glutamate receptors, and potential anchoring proteins at postsynaptic sites. Excitatory postsynaptic sites on dendritic spines contained a high concentration of F-actin that was resistant to cytochalasin D but could be depolymerized using the novel compound latrunculin A. Depolymerization of F-actin led to a 40% decrease in both the number of synaptic NMDA receptor (NMDAR1) clusters and the number of AMPA receptor (GluR1)-labeled spines. The nonsynaptic NMDA receptors appeared to remain clustered and to coalesce in cell bodies. α-Actinin-2, which binds both actin and NMDA receptors, dissociated from the receptor clusters, but PSD-95 remained associated with both the synaptic and nonsynaptic receptor clusters, consistent with a proposed cross-linking function. AMPA receptors behaved differently; on GABAergic neurons, the clusters redistributed to nonsynaptic sites, whereas on pyramidal neurons, many of the clusters appeared to disperse. Furthermore, in control neurons, AMPA receptors were detergent extractable from pyramidal cell spines, whereas AMPA receptors on GABAergic neurons and NMDA receptors were unextractable. GABA A receptors were not dependent on F-actin for the maintenance or synaptic localization of clusters. These results indicate fundamental differences in the mechanisms of receptor anchoring at postsynaptic sites, both regarding the anchoring of a single receptor (the AMPA receptor) in pyramidal cells versus GABAergic interneurons and regarding the anchoring of different receptors (AMPA vs NMDA receptors) at a single class of postsynaptic sites on pyramidal cell dendritic spines.
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Net actin disassembly at synapses appears to be slow under basal conditions, because synaptic actin punctae persist for many hours in the presence of cytochalasin D.
“Net actin disassembly at synapses appears to be slow under basal conditions, because synaptic actin punctae persist for many hours in the presence of cytochalasin D (Allison et al., 1998).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Allison et al., 1998
Actin filaments participate in membrane targeting of NMDA receptor clusters, an effect regulated by activity at NMDA receptors themselves.
“Actin filaments participate in membrane targeting of NMDA receptor clusters (Allison et al., 1998), an effect that is regulated by activity at NMDA receptors themselves (Rao and Craig, 1997).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Allison et al., 1998
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“A previous report (Allison et al., 1998) showed that incubation of cultures for 24 hr with the actin-destabilizing drug latrunculin A caused a reduction in the proportion of synaptic NMDA receptor clusters (as compared with extrasynaptic clusters).”
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- Authors
- Allison, D. W., Gelfand, V. I., Spector, I., & Craig, A. M.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Stony Brook University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-04-01
- Volume
- 18
- Issue
- 7
- Pages
- 2423-2436
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793094
- OpenAlex
- W1569092853
- Cited by
- 556
- References
- 2
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 12 · 2021: 13 · 2020: 8 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 15 · 2015: 18 · 2014: 20 · 2013: 12 · 2012: 21
- FWCI
- 17.41
- 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)
- Funders
- National Science Foundation
- National Institutes of Health (GM-52111)
- National Institute of General Medical Sciences (R01GM052111, GM52111-01)
- National Institute of Neurological Disorders and Stroke (NS33184, R01NS033184)
- 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 › Receptor Mechanisms and Signaling
- Keywords
- actin cytoskeleton, NMDA receptor, AMPA receptors, GABAA receptor, dendritic spines, latrunculin A, F-actin depolymerization, ACTN2, PSD-95, pyramidal neurons, GABAergic interneurons, receptor clustering, glutamate receptors
- MeSH terms
- Disks Large Homolog 4 Protein, Actinin, Actins, Animals, Cytoskeleton, Dendrites, Detergents, Hippocampus, Membrane Proteins, Nerve Tissue Proteins, Receptors, GABA-A, Solubility, Synapses, Thiazoles, Cytochalasin D, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Receptors, Neurotransmitter, Receptors, AMPA, Bridged Bicyclo Compounds, Heterocyclic, Nucleic Acid Synthesis Inhibitors, Intracellular Signaling Peptides and Proteins, Rats, Thiazolidines
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