Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion

Ferenc Deák, Ok Ho Shin, Ege T. Kavalali, Thomas C. Südhof

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Deletion of synaptobrevin/vesicle-associated membrane protein, the major synaptic vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE), severely decreases but does not abolish spontaneous and evoked synaptic vesicle exocytosis. We now show that the closely related R-SNARE protein cellubrevin rescues synaptic transmission in synaptobrevin-deficient neurons but that deletion of both cellubrevin and synaptobrevin does not cause a more severe decrease in exocytosis than deletion of synaptobrevin alone. We then examined the structural requirements for synaptobrevin to function in exocytosis. We found that substituting glutamine for arginine in the zero-layer of the SNARE motif did not significantly impair synaptobrevin-dependent exocytosis, whereas insertion of 12 or 24 residues between the SNARE motif and transmembrane region abolished the ability of synaptobrevin to mediate Ca 2+-evoked exocytosis. Surprisingly, however, synaptobrevin with the 12-residue but not the 24-residue insertion restored spontaneous release in synaptobrevin-deficient neurons. Our data suggest that synaptobrevin mediates Ca2+-triggered exocytosis by tight coupling of the SNARE motif to the transmembrane region and hence forcing the membranes into close proximity for fusion. Furthermore, the fusion reactions underlying evoked and spontaneous release differ mechanistically.

Original languageEnglish (US)
Pages (from-to)6668-6676
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number25
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Vesicle-Associated Membrane Protein 2
R-SNARE Proteins
Synaptic Vesicles
Exocytosis
SNARE Proteins
Vesicle-Associated Membrane Protein 3
Neurons
Glutamine
Synaptic Transmission

Keywords

  • Endocytosis
  • Exocytosis
  • Hippocampus
  • SNARE
  • Spontaneous fusion
  • Synapse
  • Synaptic vesicle recycling
  • Whole-cell patch-clamp

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion. / Deák, Ferenc; Shin, Ok Ho; Kavalali, Ege T.; Südhof, Thomas C.

In: Journal of Neuroscience, Vol. 26, No. 25, 2006, p. 6668-6676.

Research output: Contribution to journalArticle

Deák, Ferenc ; Shin, Ok Ho ; Kavalali, Ege T. ; Südhof, Thomas C. / Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 25. pp. 6668-6676.
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