SNAP-25 Regulates Spine Formation Through Postsynaptic Binding to p140Cap

Nat Commun. 2013;4:2136. doi: 10.1038/ncomms3136.

Abstract

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a member of the Soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNARE) protein family, required for exocytosis of synaptic vesicles and regulation of diverse ion channels. Here, we show that acute reduction of SNAP-25 expression leads to an immature phenotype of dendritic spines that are, consistently, less functional. Conversely, over-expression of SNAP-25 results in an increase in the density of mature, Postsynaptic Density protein 95 (PSD-95)-positive spines. The regulation of spine morphogenesis by SNAP-25 depends on the protein's ability to bind both the plasma membrane and the adaptor protein p140Cap, a key protein regulating actin cytoskeleton and spine formation. We propose that SNAP-25 allows the organization of the molecular apparatus needed for spine formation by recruiting and stabilizing p140Cap.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Adaptor Proteins, Vesicular Transport / genetics*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Disks Large Homolog 4 Protein
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental*
  • HeLa Cells
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Hippocampus / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Primary Cell Culture
  • Protein Binding
  • Protein Stability
  • Rats
  • Signal Transduction
  • Synaptosomal-Associated Protein 25 / genetics*
  • Synaptosomal-Associated Protein 25 / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SNIP protein, rat
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25