UNC-13 is required for synaptic vesicle fusion in C. elegans.
We analyzed the synaptic physiology of unc-13 mutants in the nematode C. elegans. Mutants of unc-13 had normal nervous system architecture, and the densities of synapses and postsynaptic receptors were normal at the neuromuscular junction. However, the number of synaptic vesicles at neuromuscular junctions was two- to threefold greater in unc-13 mutants than in wild-type animals. Most importantly, evoked release at both GABAergic and cholinergic synapses was almost absent in unc-13 null alleles, as determined by whole-cell, voltage-clamp techniques. Although mutant synapses had morphologically docked vesicles, these vesicles were not competent for release as assayed by spontaneous release in calcium-free solution or by the application of hyperosmotic saline. These experiments support models in which UNC-13 mediates either fusion of vesicles during exocytosis or priming of vesicles for fusion.
Richmond
J E
JE
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA.
Davis
W S
WS
Jorgensen
E M
EM
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; C083141:phorbol ester binding protein