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Nat Commun. 2014 Dec 17;5:5774. doi: 10.1038/ncomms6774.

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

Author information

1
1] Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, UK [2] Edinburgh Super-Resolution Imaging Consortium, www.esric.org.
2
1] Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh EH14 4AS, UK [2] Edinburgh Super-Resolution Imaging Consortium, www.esric.org [3] Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.
3
Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.
4
Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral Street, Glasgow G4 0RE, UK.

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.

PMID:
25517944
PMCID:
PMC4284649
DOI:
10.1038/ncomms6774
[Indexed for MEDLINE]
Free PMC Article

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