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The Journal of Neuroscience, January 1, 1998, 18(1):70-80
Synaptic Transmission Deficits in Caenorhabditis elegans
Synaptobrevin Mutants
Michael L.
Nonet1,
Owais
Saifee1,
Hongjuan
Zhao1,
James B.
Rand2, and
Liping
Wei1
1 Department of Anatomy and Neurobiology, Washington
University School of Medicine, St. Louis, Missouri 63110, and
2 Program in Molecular and Cell Biology, Oklahoma Medical
Research Foundation, Oklahoma City, Oklahoma 73104
Synaptobrevins are vesicle-associated proteins implicated in
neurotransmitter release by both biochemical studies and perturbation experiments that use botulinum toxins. To test these models in vivo, we have isolated and characterized the first
synaptobrevin mutants in metazoans and show that neurotransmission is
severely disrupted in mutant animals. Mutants lacking
snb-1 die just after completing embryogenesis. The dying
animals retain some capability for movement, although they are
extremely uncoordinated and incapable of feeding. We also have isolated
and characterized several hypomorphic snb-1 mutants.
Although fully viable, these mutants exhibit a variety of behavioral
abnormalities that are consistent with a general defect in the efficacy
of synaptic transmission. The viable mutants are resistant to the
acetylcholinesterase inhibitor aldicarb, indicating that cholinergic
transmission is impaired. Extracellular recordings from pharyngeal
muscle also demonstrate severe defects in synaptic transmission in the
mutants. The molecular lesions in the hypomorphic alleles reside on the
hydrophobic face of a proposed amphipathic-helical region implicated
biochemically in interacting with the t-SNAREs syntaxin and SNAP-25.
Finally, we demonstrate that double mutants lacking both the v-SNAREs
synaptotagmin and snb-1 are phenotypically similar to
snb-1 mutants and less severe than syntaxin mutants. Our
work demonstrates that synaptobrevin is essential for viability and is
required for functional synaptic transmission. However, our analysis
also suggests that transmitter release is not completely eliminated by
removal of either one or both v-SNAREs.
Key words:
synaptobrevin; VAMP; exocytosis; synaptic vesicle
protein; mutants; Caenorhabditis elegans; v-SNARE
Copyright © 1998 Society for Neuroscience 0270-6474/98/18170-11$05.00/0
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