Abstract
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Animals
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Animals, Newborn
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Biophysics
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Cells, Cultured
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Electric Stimulation
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Excitatory Amino Acid Antagonists / pharmacology
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Exocytosis / drug effects
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Exocytosis / physiology*
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Gene Transfer Techniques
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Glycine / pharmacology
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Hippocampus / cytology
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In Vitro Techniques
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology*
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Membrane Fusion / drug effects
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Membrane Fusion / physiology*
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Mice
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Mice, Inbred C57BL
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Neurons / drug effects
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Neurons / physiology*
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Patch-Clamp Techniques
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Protein Binding / drug effects
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Protein Binding / genetics
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Qa-SNARE Proteins / metabolism
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Quinoxalines / pharmacology
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Receptors, AMPA / metabolism
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Receptors, Transferrin / metabolism
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SNARE Proteins / genetics
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SNARE Proteins / metabolism*
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Syntaxin 1 / metabolism
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Vesicle-Associated Membrane Protein 2 / metabolism
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Vesicular Transport Proteins / metabolism
Substances
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Excitatory Amino Acid Antagonists
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Qa-SNARE Proteins
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Quinoxalines
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Receptors, AMPA
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Receptors, Transferrin
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SNARE Proteins
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Syntaxin 1
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Vesicle-Associated Membrane Protein 2
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Vesicular Transport Proteins
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Glycine
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glutamate receptor ionotropic, AMPA 1