LTP requires a unique postsynaptic SNARE fusion machinery

Neuron. 2013 Feb 6;77(3):542-58. doi: 10.1016/j.neuron.2012.11.029.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Animals, Newborn
  • Biophysics
  • Cells, Cultured
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Gene Transfer Techniques
  • Glycine / pharmacology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Membrane Fusion / drug effects
  • Membrane Fusion / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Qa-SNARE Proteins / metabolism
  • Quinoxalines / pharmacology
  • Receptors, AMPA / metabolism
  • Receptors, Transferrin / metabolism
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*
  • Syntaxin 1 / metabolism
  • Vesicle-Associated Membrane Protein 2 / metabolism
  • Vesicular Transport Proteins / metabolism

Substances

  • Excitatory Amino Acid Antagonists
  • Qa-SNARE Proteins
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, Transferrin
  • SNARE Proteins
  • Syntaxin 1
  • Vesicle-Associated Membrane Protein 2
  • Vesicular Transport Proteins
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Glycine
  • glutamate receptor ionotropic, AMPA 1