An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming (original) (raw)

Nature volume 412, pages 338–341 (2001)Cite this article

Abstract

The priming step of synaptic vesicle exocytosis is thought to require the formation of the SNARE complex, which comprises the proteins synaptobrevin, SNAP-25 and syntaxin1,2,3. In solution syntaxin adopts a default, closed configuration that is incompatible with formation of the SNARE complex4. Specifically, the amino terminus of syntaxin binds the SNARE motif and occludes interactions with the other SNARE proteins. The N terminus of syntaxin also binds the presynaptic protein UNC-13 (ref. 5). Studies in mouse, Drosophila and Caenorhabditis elegans suggest that UNC-13 functions at a post-docking step of exocytosis, most likely during synaptic vesicle priming6,7,8. Therefore, UNC-13 binding to the N terminus of syntaxin may promote the open configuration of syntaxin9. To test this model, we engineered mutations into C. elegans syntaxin that cause the protein to adopt the open configuration constitutively4. Here we demonstrate that the open form of syntaxin can bypass the requirement for UNC-13 in synaptic vesicle priming. Thus, it is likely that UNC-13 primes synaptic vesicles for fusion by promoting the open configuration of syntaxin.

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Acknowledgements

We thank M. Nonet for providing unc-64(js115), RAB-3 antibodies and the plasmid pTX21; R. Hosono for providing UNC-18 antibodies; A. Rose for providing the unc-13(s69) allele; and P. Sengupta for the Punc-122::GFP plasmid. We also thank K. Broadie for critical review of this manuscript. This work was supported by NIH grants to J.E.R. and E.M.J.

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Author notes

  1. Janet E. Richmond and Robby M. Weimer: These authors contributed equally to this work
  2. Correspondence and requests for materials should be addressed to E.M.J.

Authors and Affiliations

  1. Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, 84112-0840, Utah, USA
    Janet E. Richmond, Robby M. Weimer & Erik M. Jorgensen

Authors

  1. Janet E. Richmond
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  2. Robby M. Weimer
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  3. Erik M. Jorgensen
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Correspondence toErik M. Jorgensen.

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Richmond, J., Weimer, R. & Jorgensen, E. An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming.Nature 412, 338–341 (2001). https://doi.org/10.1038/35085583

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