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Publication : The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones.

First Author  Imig C Year  2014
Journal  Neuron Volume  84
Issue  2 Pages  416-31
PubMed ID  25374362 Mgi Jnum  J:218225
Mgi Id  MGI:5617001 Doi  10.1016/j.neuron.2014.10.009
Citation  Imig C, et al. (2014) The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron 84(2):416-31
abstractText  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.
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