The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones
Research output: Contribution to journal › Journal article › Research › peer-review
Synaptic vesicle docking, priming, and fusion at active zones are orchestrated by a complex molecular machinery. We employed hippocampal organotypic slice cultures from mice lacking key presynaptic proteins, cryofixation, and three-dimensional electron tomography to study the mechanism of synaptic vesicle docking in the same experimental setting, with high precision, and in a near-native state. We dissected previously indistinguishable, sequential steps in synaptic vesicle active zone recruitment (tethering) and membrane attachment (docking) and found that vesicle docking requires Munc13/CAPS family priming proteins and all three neuronal SNAREs, but not Synaptotagmin-1 or Complexins. Our data indicate that membrane-attached vesicles comprise the readily releasable pool of fusion-competent vesicles and that synaptic vesicle docking, priming, and trans-SNARE complex assembly are the respective morphological, functional, and molecular manifestations of the same process, which operates downstream of vesicle tethering by active zone components.
Original language | English |
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Journal | Neuron |
Volume | 84 |
Issue number | 2 |
Pages (from-to) | 416-31 |
Number of pages | 16 |
ISSN | 0896-6273 |
DOIs | |
Publication status | Published - 22 Oct 2014 |
Externally published | Yes |
- Animals, Hippocampus/metabolism, Membrane Fusion/physiology, Mice, Neurons/metabolism, SNARE Proteins/metabolism, Synapses/metabolism, Synaptic Transmission/physiology, Synaptic Vesicles/metabolism
Research areas
ID: 237698103