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A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans

Abstract

Acetylcholine, a major excitatory neurotransmitter in Caenorhabditis elegans, is transported into synaptic vesicles by the vesicular acetylcholine transporter encoded by unc-17. The abnormal behavior of unc-17(e245) mutants, which have a glycine-to-arginine substitution in a transmembrane domain, is markedly improved by a mutant synaptobrevin with an isoleucine-to-aspartate substitution in its transmembrane domain. These results suggest an association of vesicular soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) components with vesicular neurotransmitter transporters.

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Figure 1: unc-17(e245) is suppressed by the synaptobrevin mutant sup-8(e1563).
Figure 2: Suppression of unc-17(e245) behavioral deficiencies varies with the position of the substituted mutation in the transmembrane domain of SNARE complex components.
Figure 3: SNB-1(I97D) restores VAChT/UNC-17 abundance in unc-17(e245) mutants.

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Acknowledgements

We thank B. Reinhart, W. Li, C. Wolkow, J. Kaplan, B. Seed and members of the Ruvkun lab for helpful discussions and suggestions; and P. Delerme, J. Xu, L. Xue and S. Joksimovic for their technical assistance. The Caenorhabditis Genetic Center, funded by the US National Institutes of Health National Center for Research Resources, provided some strains.

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Correspondence to Gary Ruvkun.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

sup-8 (e1563) corresponds to an allele of synaptobrevin. (PDF 211 kb)

Supplementary Fig. 2

Aldicarb sensitivity in transgenic animals over-expressing VAChT/UNC-17. (PDF 2201 kb)

Supplementary Table 1

Thrashing rates of unc-17(e245) expressing snb-1(e1563) at different concentrations. (PDF 94 kb)

Supplementary Table 2

Rescue of snb-1(js124). (PDF 93 kb)

Supplementary Table 3

Quantification of Anti-VAChT/UNC-17 staining. (PDF 97 kb)

Supplementary Methods (PDF 99 kb)

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Sandoval, G., Duerr, J., Hodgkin, J. et al. A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans. Nat Neurosci 9, 599–601 (2006). https://doi.org/10.1038/nn1685

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