A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking

Nat Neurosci. 2010 Mar;13(3):338-43. doi: 10.1038/nn.2488. Epub 2010 Jan 31.

Abstract

Regulated exocytosis is essential for many biological processes and many components of the protein trafficking machinery are ubiquitous. However, there are also exceptions, such as SNAP-25, a neuron-specific SNARE protein that is essential for synaptic vesicle release from presynaptic nerve terminals. In contrast, SNAP-23 is a ubiquitously expressed SNAP-25 homolog that is critical for regulated exocytosis in non-neuronal cells. However, the role of SNAP-23 in neurons has not been elucidated. We found that SNAP-23 was enriched in dendritic spines and colocalized with constituents of the postsynaptic density, whereas SNAP-25 was restricted to axons. In addition, loss of SNAP-23 using genetically altered mice or shRNA targeted to SNAP-23 led to a marked decrease in NMDA receptor surface expression and NMDA receptor currents, whereas loss of SNAP-25 did not. SNAP-23 is therefore important for the functional regulation of postsynaptic glutamate receptors.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Cell Line
  • Cell Membrane / metabolism
  • Dendrites / physiology
  • Dendritic Spines / physiology
  • Hippocampus / physiology
  • Humans
  • In Vitro Techniques
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • Neurons / physiology*
  • Qb-SNARE Proteins / genetics
  • Qb-SNARE Proteins / metabolism*
  • Qc-SNARE Proteins / genetics
  • Qc-SNARE Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / physiology*
  • Synaptosomal-Associated Protein 25 / genetics
  • Synaptosomal-Associated Protein 25 / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Snap23 protein, mouse
  • Snap23 protein, rat
  • Snap25 protein, mouse
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Vesicular Transport Proteins