A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion

Deirdre M. Kavanagh, Annya M. Smyth, Kirsty J. Martin, Alison Dun, Euan R. Brown, Sarah Gordon, Karen J. Smillie, Luke H. Chamberlain, Rhodri S. Wilson, Lei Yang, Weiping Lu, Michael A. Cousin, Colin Rickman, Rory R. Duncan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Neuronal synapses are among the most scrutinized of cellular systems, serving as a model for all membrane trafficking studies. Despite this, synaptic biology has proven difficult to interrogate directly in situ due to the small size and dynamic nature of central synapses and the molecules within them. Here we determine the spatial and temporal interaction status of presynaptic proteins, imaging large cohorts of single molecules inside active synapses. Measuring rapid interaction dynamics during synaptic depolarization identified the small number of syntaxin1a and munc18-1 protein molecules required to support synaptic vesicle exocytosis. After vesicle fusion and subsequent SNARE complex disassembly, a prompt switch in syntaxin1a and munc18-1-binding mode, regulated by charge alteration on the syntaxin1a N-terminal, sequesters monomeric syntaxin1a from other disassembled fusion complex components, preventing ectopic SNARE complex formation, readying the synapse for subsequent rounds of neurotransmission.
LanguageEnglish
Article number5774
Number of pages14
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 17 Dec 2014

Fingerprint

synapses
Exocytosis
Synapses
SNARE Proteins
Fusion reactions
fusion
Molecules
Munc18 Proteins
molecules
Depolarization
proteins
Synaptic Vesicles
biology
Switches
Synaptic Transmission
depolarization
Membranes
Imaging techniques
switches
interactions

Keywords

  • cellular systems
  • synaptic biology
  • neurotransmission

Cite this

Kavanagh, D. M., Smyth, A. M., Martin, K. J., Dun, A., Brown, E. R., Gordon, S., ... Duncan, R. R. (2014). A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion. Nature Communications, 5, [5774]. https://doi.org/10.1038/ncomms6774
Kavanagh, Deirdre M. ; Smyth, Annya M. ; Martin, Kirsty J. ; Dun, Alison ; Brown, Euan R. ; Gordon, Sarah ; Smillie, Karen J. ; Chamberlain, Luke H. ; Wilson, Rhodri S. ; Yang, Lei ; Lu, Weiping ; Cousin, Michael A. ; Rickman, Colin ; Duncan, Rory R. / A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion. In: Nature Communications. 2014 ; Vol. 5.
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Kavanagh, DM, Smyth, AM, Martin, KJ, Dun, A, Brown, ER, Gordon, S, Smillie, KJ, Chamberlain, LH, Wilson, RS, Yang, L, Lu, W, Cousin, MA, Rickman, C & Duncan, RR 2014, 'A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion' Nature Communications, vol. 5, 5774. https://doi.org/10.1038/ncomms6774

A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion. / Kavanagh, Deirdre M.; Smyth, Annya M.; Martin, Kirsty J.; Dun, Alison; Brown, Euan R.; Gordon, Sarah; Smillie, Karen J.; Chamberlain, Luke H.; Wilson, Rhodri S.; Yang, Lei; Lu, Weiping; Cousin, Michael A.; Rickman, Colin; Duncan, Rory R.

In: Nature Communications, Vol. 5, 5774, 17.12.2014.

Research output: Contribution to journalArticle

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AU - Dun, Alison

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AU - Rickman, Colin

AU - Duncan, Rory R.

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