The Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones

作者：Imig Cordelia; Min Sang Won; Krinner Stefanie; Arancillo Marife; Rosenmund Christian; Suedhof Thomas C; Rhee JeongSeop; Brose Nils^*; Cooper Benjamin H

来源：Neuron, 2014, 84(2): 416-431.

DOI：10.1016/j.neuron.2014.10.009

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.

• 出版日期2014-10-22