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Elife. 2012 Dec 13;1:e00109. doi: 10.7554/eLife.00109.

Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.

Author information

1
Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Structural Biology, Photon Science and Howard Hughes Medical Institute , Stanford University , Stanford , USA.

Abstract

The molecular underpinnings of synaptic vesicle fusion for fast neurotransmitter release are still unclear. Here, we used a single vesicle-vesicle system with reconstituted SNARE and synaptotagmin-1 proteoliposomes to decipher the temporal sequence of membrane states upon Ca(2+)-injection at 250-500 μM on a 100-ms timescale. Furthermore, detailed membrane morphologies were imaged with cryo-electron microscopy before and after Ca(2+)-injection. We discovered a heterogeneous network of immediate and delayed fusion pathways. Remarkably, all instances of Ca(2+)-triggered immediate fusion started from a membrane-membrane point-contact and proceeded to complete fusion without discernible hemifusion intermediates. In contrast, pathways that involved a stable hemifusion diaphragm only resulted in fusion after many seconds, if at all. When complexin was included, the Ca(2+)-triggered fusion network shifted towards the immediate pathway, effectively synchronizing fusion, especially at lower Ca(2+)-concentration. Synaptic proteins may have evolved to select this immediate pathway out of a heterogeneous network of possible membrane fusion pathways.DOI:http://dx.doi.org/10.7554/eLife.00109.001.

KEYWORDS:

Other; SNARE; complexin; neurotransmitter release; synaptic vesicle fusion; synaptotagmin

PMID:
23240085
PMCID:
PMC3514886
DOI:
10.7554/eLife.00109
[Indexed for MEDLINE]
Free PMC Article

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