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

  • Author(s): Diao, Jiajie
  • Grob, Patricia
  • Cipriano, Daniel J
  • Kyoung, Minjoung
  • Zhang, Yunxiang
  • Shah, Sachi
  • Nguyen, Amie
  • Padolina, Mark
  • Srivastava, Ankita
  • Vrljic, Marija
  • Shah, Ankita
  • Nogales, Eva
  • Chu, Steven
  • Brunger, Axel T
  • et al.
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.

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