Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines
Open accessAbstract
Changes in postsynaptic membrane composition underlie many forms of learning-related synaptic plasticity in the brain. At excitatory glutamatergic synapses, fusion of intracellular vesicles at or near the postsynaptic plasma membrane is critical for dendritic spine morphology, retrograde synaptic signaling, and long-term synaptic plasticity. Whereas the molecular machinery for exocytosis in presynaptic terminals has been defined in detail, little is known about the location, kinetics, regulation, or molecules involved in postsynaptic exocytosis. Here, we show that an exocytic domain adjacent to the postsynaptic density (PSD) enables fusion of large, AMPA receptor-containing recycling compartments during elevated synaptic activity. Exocytosis occurs at microdomains enriched in the plasma membrane t-SNARE syntaxin 4 (Stx4), and disruption of Stx4 impairs both spine exocytosis and long-term potentiation (LTP) at hippocampal synapses. Thus, Stx4 defines an exocytic zone that directs membrane fusion for postsynaptic plasticity, revealing a novel specialization for local membrane traffic in dendritic spines.
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By tagging AMPARs with a pH-sensitive tag (SEP-GluA1), insertion of AMPARs into the surface membrane can be directly visualized during LTP-inducing protocols.
“By tagging AMPARs with a pH-sensitive tag (SEP-GluA1), the insertion of AMPARs into the surface membrane can be directly visualized during LTP-inducing protocols (249, 250, 335, 337, 338, 340).”
From Synaptic memory and CaMKII (2023) · cites this paper as [338]
The Results section, “AMPA Receptors are Stably Inserted Into the Spine Plasma Membrane Via Fusion of Spine Endosomes” (page unavailable), reports direct imaging of SEP-GluR1 insertion after Bic/Gly stimulation. The paper describes Bic/Gly as increasing network activity; its separately described LTP-induction protocol was used for electrophysiology, not SEP-GluR1 imaging. It therefore supports the visualization claim but not specifically visualization during a protocol it identifies as LTP-inducing. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBlocking postsynaptic exocytosis by a variety of means blocks LTP/sLTP.
“Numerous studies have shown that blocking postsynaptic exocytosis by a variety of means blocks LTP/sLTP (195, 249, 250, 332–338).”
From Synaptic memory and CaMKII (2023) · cites this paper as [338]
Stx-4 is reported to be required for LTP.
“while on the other hand Stx-4 is reported to be required for LTP (336, 338).”
From Synaptic memory and CaMKII (2023) · cites this paper as [338]
Exocytic trafficking from recycling compartments contributes to dendritic spine growth in response to activity.
“Exocytic trafficking from recycling compartments contributes to dendritic spine growth in response to activity (Park et al, 2006;Kennedy et al, 2010)”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Kennedy et al, 2010
Coupled with the potential of dendrites for activity-stimulated exocytosis, such a phenomenon could account for the perineuronal deposits of oligomers seen in Figure 1.
“Coupled with the potential of dendrites for activity-stimulated exocytosis (Kennedy et al., 2010), such a phenomenon could account for the “perineuronal deposits” of oligomers seen in Figure 1 (Lacor et al., 2004).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Kennedy et al., 2010
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- Authors
- Kennedy, M. J., Davison, I. G., Robinson, C. G., & Ehlers, M. D.
- Affiliations
- Duke Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ehlers, Michael D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 141
- Issue
- 3
- Pages
- 524-535
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2874581
- OpenAlex
- W1982810155
- Cited by
- 294
- References
- 46
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 13 · 2023: 10 · 2022: 15 · 2021: 19 · 2020: 22 · 2019: 11 · 2018: 20 · 2017: 16 · 2016: 15 · 2015: 17 · 2014: 27 · 2013: 31 · 2012: 29
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG024492)
- National Institute of Mental Health (R01MH064748)
- National Institute of Neurological Disorders and Stroke (R01NS047574)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- syntaxin 4, dendritic spines, synaptic plasticity, long-term potentiation, postsynaptic density, t-SNARE, membrane fusion, hippocampal synapses
- MeSH terms
- Animals, Cell Membrane, Cells, Cultured, Exocytosis, Hippocampus, Humans, Mice, Inbred C57BL, Endosomes, Dendritic Spines, SNARE Proteins, Qa-SNARE Proteins, Mice, Rats, Gene Knockdown Techniques
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