Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23

Cell. 2003 Jul 11;114(1):75-86. doi: 10.1016/s0092-8674(03)00477-x.


The SNARE complex, consisting of synaptobrevin, syntaxin, and SNAP-25, is essential for calcium-triggered exocytosis in neurosecretory cells. Little is known, however, about how developmentally regulated isoforms and other cognate SNARE components regulate vesicular fusion. To address this question, we examined neuroexocytosis from chromaffin cells of Snap25 null mice rescued by the two splice variants SNAP-25a and SNAP-25b and the ubiquitously expressed homolog SNAP-23. In the absence of SNAP-25, vesicle docking persisted, but primed vesicle pools were empty and fast calcium-triggered release abolished. Single vesicular fusion events showed normal characteristics, except for a shorter duration of the fusion pore. Overexpression of SNAP-25a, SNAP-25b, and SNAP-23 resulted in three distinct phenotypes; SNAP-25b induced larger primed vesicle pools than SNAP-25a, whereas SNAP-23 did not support a standing pool of primed vesicles. We conclude that three alternative SNARE components support exocytosis, but they differ in their ability to stabilize vesicles in the primed state.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chromaffin Cells / metabolism*
  • Chromaffin Cells / ultrastructure
  • Exocytosis / genetics*
  • Fetus
  • Membrane Fusion / genetics
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Neurosecretion / genetics*
  • Neurosecretory Systems / metabolism*
  • Neurosecretory Systems / ultrastructure
  • Phenotype
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Secretory Vesicles / metabolism*
  • Secretory Vesicles / ultrastructure
  • Synaptosomal-Associated Protein 25


  • Carrier Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • SNAP23 protein, human
  • Snap23 protein, mouse
  • Snap25 protein, mouse
  • Synaptosomal-Associated Protein 25
  • Calcium