LTP Requires a Unique Postsynaptic SNARE Fusion Machinery
Open accessAbstract
Membrane fusion during exocytosis is mediated by assemblies of SNARE (soluble NSF-attachment protein receptor) and SM (Sec1/Munc18-like) proteins. The SNARE/SM proteins involved in vesicle fusion during neurotransmitter release are well understood, whereas little is known about the protein machinery that mediates activity-dependent AMPA receptor (AMPAR) exocytosis during long-term potentiation (LTP). Using direct measurements of LTP in acute hippocampal slices and an in vitro LTP model of stimulated AMPAR exocytosis, we demonstrate that the Q-SNARE proteins syntaxin-3 and SNAP-47 are required for regulated AMPAR exocytosis during LTP but not for constitutive basal AMPAR exocytosis. In contrast, the R-SNARE protein synaptobrevin-2/VAMP2 contributes to both regulated and constitutive AMPAR exocytosis. Both the central complexin-binding and the N-terminal Munc18-binding sites of syntaxin-3 are essential for its postsynaptic role in LTP. Thus, postsynaptic exocytosis of AMPARs during LTP is mediated by a unique fusion machinery that is distinct from that used during presynaptic neurotransmitter release.
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Blocking 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 [334]
The Results section, “Postsynaptic Syntaxin-3 is Required for AMPAR Delivery During LTP” (page unavailable), reports that postsynaptic syntaxin-3 knockdown blocked the cultured LTP-like response but impaired, rather than abolished, LTP in acute slices. The Results section on SNAP-47 likewise reports impaired slice LTP. These findings support the role of postsynaptic exocytosis in LTP, but not an unqualified claim that the interventions blocked LTP or structural LTP (sLTP). (LLM, conf=0.83)
Experimental — accuracy not yet measuredStx-3 is reported to be required for LTP.
“On the one hand Stx-3 is reported to be required for LTP (Ref. 334, but see Ref. 339)”
From Synaptic memory and CaMKII (2023) · cites this paper as [334]
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- Authors
- Jurado, S., Goswami, D., Zhang, Y., Molina, A. J. M., Südhof, T. C., & Malenka, R. C.
- Affiliations
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Malenka, Robert C.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 77
- Issue
- 3
- Pages
- 542-558
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3569727
- OpenAlex
- W2012632097
- Cited by
- 232
- References
- 84
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 11 · 2023: 24 · 2022: 12 · 2021: 15 · 2020: 15 · 2019: 14 · 2018: 26 · 2017: 28 · 2016: 22 · 2015: 15 · 2014: 13 · 2013: 13
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institutes of Health (MH063394, MH086403)
- Ministerio de Educación, Cultura y Deporte
- 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
- long-term potentiation, SNARE proteins, syntaxin 3, Munc18, complexin, hippocampus, regulated exocytosis
- MeSH terms
- Animals, Animals, Newborn, Biophysics, Cells, Cultured, Electric Stimulation, Exocytosis, Glycine, Hippocampus, Membrane Fusion, Mice, Inbred C57BL, Neurons, Protein Binding, Quinoxalines, Receptors, Transferrin, Long-Term Potentiation, Gene Transfer Techniques, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Vesicular Transport Proteins, SNARE Proteins, Qa-SNARE Proteins, Syntaxin 1, Vesicle-Associated Membrane Protein 2, Mice, In Vitro Techniques
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