Open Syntaxin Docks Synaptic Vesicles

Open Access
Publisher Website
Google Scholar
Abstract
Synaptic vesicles dock to the plasma membrane at synapses to facilitate rapid exocytosis. Docking was originally proposed to require the soluble N-ethylmaleimide–sensitive fusion attachment protein receptor (SNARE) proteins; however, perturbation studies suggested that docking was independent of the SNARE proteins. We now find that the SNARE protein syntaxin is required for docking of all vesicles at synapses in the nematode Caenorhabditis elegans. The active zone protein UNC-13, which interacts with syntaxin, is also required for docking in the active zone. The docking defects in unc-13 mutants can be fully rescued by overexpressing a constitutively open form of syntaxin, but not by wild-type syntaxin. These experiments support a model for docking in which UNC-13 converts syntaxin from the closed to the open state, and open syntaxin acts directly in docking vesicles to the plasma membrane. These data provide a molecular basis for synaptic vesicle docking. Like Olympic swimmers crouched on their starting blocks, synaptic vesicles prepare for fusion with the neuronal plasma membrane long before the starting gun fires. This preparation enables vesicles to fuse rapidly, synchronously, and in the correct place when the signal finally arrives. A well-known but poorly understood part of vesicle preparation is docking, in which vesicles prepare for release by attaching to the plasma membrane at the eventual site of release. Here, we outline a molecular mechanism for docking. Using a combination of genetics and electron microscopy, we find that docking requires two proteins: the cytoplasmic protein UNC-13 and the plasma membrane protein syntaxin. Syntaxin is known to form two configurations, closed and open. We find that the open form of syntaxin can bypass the docking function of UNC-13, while the closed form cannot. These experiments suggest that docking is the attachment of synaptic vesicles to syntaxin; that syntaxin must be open for this attachment to occur; and that UNC-13′s role in docking is to promote open syntaxin.