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An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming

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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Figure 1: Expression of the constitutively open form of syntaxin rescued the syntaxin null unc-64(js115).
Figure 2: Open syntaxin failed to rescue mutants of the alpha subunit of the N-type voltage-gated calcium channel, UNC-2.
Figure 3: The open form of syntaxin rescues the unc-13(s69) mutant.

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References

  1. Sollner, T. et al. SNAP receptors implicated in vesicle targeting and fusion. Nature 362, 318–324 (1993).

    ADS  CAS  PubMed  Google Scholar 

  2. Broadie, K. et al. Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 15, 663–673 (1995).

    CAS  PubMed  Google Scholar 

  3. Hanson, P. I., Roth, R., Morisaki, H., Jahn, R. & Heuser, J. E. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 90, 523–535 (1997).

    CAS  PubMed  Google Scholar 

  4. Dulubova, I. et al. A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J. 18, 4372–4382 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Betz, A., Okamoto, M., Benseler, F. & Brose, N. Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin. J. Biol. Chem. 272, 2520–2526 (1997).

    CAS  PubMed  Google Scholar 

  6. Augustin, I., Rosenmund, C., Sudhof, T. C. & Brose, N. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400, 457–461 (1999).

    ADS  CAS  PubMed  Google Scholar 

  7. Aravamudan, B., Fergestad, T., Davis, W. S., Rodesch, C. K. & Broadie, K. Drosophila Unc-13 is essential for synaptic transmission. Nature Neurosci. 2, 965–971 (1999).

    CAS  PubMed  Google Scholar 

  8. Richmond, J. E., Davis, W. S. & Jorgensen, E. M. UNC-13 is required for synaptic vesicle fusion in C. elegans. Nature Neurosci. 2, 959–964 (1999).

    CAS  PubMed  Google Scholar 

  9. Brose, N., Rosenmund, C. & Rettig, J. Regulation of transmitter release by Unc-13 and its homologues. Curr. Opin. Neurobiol. 10, 303–311 (2000).

    CAS  PubMed  Google Scholar 

  10. Saifee, O., Wei, L. & Nonet, M. L. The Caenorhabditis elegans unc-64 locus encodes a syntaxin that interacts genetically with synaptobrevin. Mol. Biol. Cell 9, 1235–1252 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Richmond, J. E. & Jorgensen, E. M. One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction. Nature Neurosci. 2, 791–797 (1999).

    CAS  PubMed  Google Scholar 

  12. Nonet, M. L., Saifee, O., Zhao, H., Rand, J. B. & Wei, L. Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants. J. Neurosci. 18, 70–80 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Schafer, W. R. & Kenyon, C. J. A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans. Nature 375, 73–78 (1995).

    ADS  CAS  PubMed  Google Scholar 

  14. Kohn, R. E. et al. Expression of multiple UNC-13 proteins in the C. elegans nervous system. Mol. Biol. Cell 11, 3441–3452 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Maruyama, I. N. & Brenner, S. A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 88, 5729–5733 (1991).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brose, N., Hofmann, K., Hata, Y. & Sudhof, T. C. Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins. J. Biol. Chem. 270, 25273–2580 (1995).

    CAS  PubMed  Google Scholar 

  17. Ashery, U. et al. Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells. EMBO J. 19, 3586–3596 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Xu, T. et al. Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis. Cell 99, 713–722 (1999).

    CAS  PubMed  Google Scholar 

  19. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Miyabayashi, T., Palfreyman, M. T., Sluder, A. E., Slack, F. & Sengupta, P. Expression and function of members of a divergent nuclear receptor family in Caenorhabditis elegans. Dev. Biol. 215, 314–331 (1999).

    CAS  PubMed  Google Scholar 

  21. Miller, K. G. et al. A genetic selection for Caenorhabditis elegans synaptic transmission mutants. Proc. Natl Acad. Sci. USA 93, 12593–12598 (1996).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Thomas, J. H. Genetic analysis of defecation in Caenorhabditis elegans. Genetics 124, 855–872 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

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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

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  1. Janet E. Richmond
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Correspondence to Erik 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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