A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis

Jiong Tang, Anton Maximov, Ok Ho Shin, Han Dai, Josep Rizo, Thomas C. Südhof

Research output: Contribution to journalArticle

306 Citations (Scopus)

Abstract

Ca2+ binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca2+-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca2+ binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca2+-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca2+-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca2+-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca2+-triggered neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)1175-1187
Number of pages13
JournalCell
Volume126
Issue number6
DOIs
StatePublished - Sep 22 2006
Externally publishedYes

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Synaptotagmin I
SNARE Proteins
Synaptic Vesicles
Exocytosis
Switches
Neurotransmitter Agents
Fusion reactions
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Tang, J., Maximov, A., Shin, O. H., Dai, H., Rizo, J., & Südhof, T. C. (2006). A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis. Cell, 126(6), 1175-1187. https://doi.org/10.1016/j.cell.2006.08.030

A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis. / Tang, Jiong; Maximov, Anton; Shin, Ok Ho; Dai, Han; Rizo, Josep; Südhof, Thomas C.

In: Cell, Vol. 126, No. 6, 22.09.2006, p. 1175-1187.

Research output: Contribution to journalArticle

Tang, J, Maximov, A, Shin, OH, Dai, H, Rizo, J & Südhof, TC 2006, 'A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis', Cell, vol. 126, no. 6, pp. 1175-1187. https://doi.org/10.1016/j.cell.2006.08.030
Tang J, Maximov A, Shin OH, Dai H, Rizo J, Südhof TC. A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis. Cell. 2006 Sep 22;126(6):1175-1187. https://doi.org/10.1016/j.cell.2006.08.030
Tang, Jiong ; Maximov, Anton ; Shin, Ok Ho ; Dai, Han ; Rizo, Josep ; Südhof, Thomas C. / A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis. In: Cell. 2006 ; Vol. 126, No. 6. pp. 1175-1187.
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