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Open Access Publications from the University of California

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.

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:

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