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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Caenorhabditis elegans* / cytology
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Caenorhabditis elegans* / metabolism
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Carrier Proteins
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Cell Membrane / metabolism
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Cell Membrane / ultrastructure
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Cell Shape
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Exocytosis / physiology
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Membrane Fusion / physiology*
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Mosaicism
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Neuromuscular Junction / physiology
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Neuromuscular Junction / ultrastructure
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Neuromuscular Nondepolarizing Agents / pharmacology
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Neurons / cytology
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Neurons / physiology
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Patch-Clamp Techniques
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Qa-SNARE Proteins / genetics
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Qa-SNARE Proteins / metabolism*
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Qa-SNARE Proteins / ultrastructure
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Synapses / drug effects
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Synapses / metabolism*
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Synapses / ultrastructure
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Synaptic Vesicles / metabolism*
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Synaptic Vesicles / ultrastructure
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Tubocurarine / pharmacology
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gamma-Aminobutyric Acid / metabolism
Substances
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Neuromuscular Nondepolarizing Agents
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Qa-SNARE Proteins
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Recombinant Fusion Proteins
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phorbol ester binding protein
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gamma-Aminobutyric Acid
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Tubocurarine