title: Defects in synaptic vesicle docking in unc-18 mutants.
abstract: Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.
authors.affiliation: Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA.
authors.forename: Robby M
authors.initials: RM
authors.lastname: Weimer
authors.forename: Janet E
authors.initials: JE
authors.lastname: Richmond
authors.forename: Warren S
authors.initials: WS
authors.lastname: Davis
authors.forename: Gayla
authors.initials: G
authors.lastname: Hadwiger
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nonet
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D004558:Electric Stimulation; D005089:Exocytosis / Q000502:physiology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008561:Membrane Fusion / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D023421:Models, Animal; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009469:Neuromuscular Junction / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D010750:Phosphoproteins; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D018079:Receptors, GABA; D011993:Recombinant Fusion Proteins; C082636:Unc-18 protein, C elegans; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid