Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Complexin arrests a neighbor

Nature Structural & Molecular Biology volume 18, pages 861–863 (2011)Cite this article

Subjects

Mechanistic details about complexin's contradictory double life as both a facilitator and an inhibitor of SNARE-mediated synaptic vesicle fusion have been challenging to uncover. A series of studies in this issue addresses the problem by revealing a switchable complexin conformation in which fusion arrest occurs when complexin clamps neighboring SNAREs.

First, a bit more information about the complexin puzzle (which is expertly reviewed elsewhere4) is warranted. Increasing or decreasing the complexin concentration by overexpression or knockdown reduces exocytosis in neuron-based assays. These observations are difficult to reconcile unless both stimulatory and inhibitory functions for complexin are accepted. Total knockout of complexin in mouse5 and fly6 neurons dramatically reduces stimulated neurotransmission, suggesting a positive role for complexin. But Ca2+-independent secretion also increases in the fly deletions, suggesting that complexin clamps spontaneous release. A clamping role is also indicated by in vitro studies7,8,9, because adding complexin usually inhibits fusion in SNARE-reconstituted liposome or flipped SNARE fusion assays (in which cells are engineered to express outward facing SNAREs on their surface membrane). Overall, these contradictory results indicate that complexin can both facilitate and inhibit neurotransmitter release, probably acting at different times as vesicles are docked, primed and fused.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Complexin modulates SNARE-driven membrane fusion of synaptic vesicles.
Figure 2: Schematics illustrating the configuration of complexin.

References

  1. Li, F. et al. Nat. Struct. Mol. Biol. 18, 941–946 (2011).

    CAS  Article  Google Scholar 

  2. Kümmel, D. et al. Nat. Struct. Mol. Biol. 18, 927–933 (2011).

    Article  Google Scholar 

  3. Krishnakumar, S.S. et al. Nat. Struct. Mol. Biol. 18, 934–940 (2011).

    CAS  Article  Google Scholar 

  4. Brose, N. Traffic 9, 1403–1413 (2008).

    CAS  Article  Google Scholar 

  5. Reim, K. et al. Cell 104, 71–81 (2001).

    CAS  Article  Google Scholar 

  6. Huntwork, S. & Littleton, J.T. Nat. Neurosci. 10, 1235–1237 (2007).

    CAS  Article  Google Scholar 

  7. Giraudo, C.G., Eng, W.S., Melia, T.J. & Rothman, J.E. Science 313, 676–680 (2006).

    CAS  Article  Google Scholar 

  8. Schaub, J.R., Lu, X., Doneske, B., Shin, Y.K. & McNew, J.A. Nat. Struct. Mol. Biol. 13, 748–750 (2006).

    CAS  Article  Google Scholar 

  9. Tang, J. et al. Cell 126, 1175–1187 (2006).

    CAS  Article  Google Scholar 

  10. Chen, X. et al. Neuron 33, 397–409 (2002).

    CAS  Article  Google Scholar 

  11. Xue, M. et al. Nat. Struct. Mol. Biol. 14, 949–958 (2007).

    CAS  Article  Google Scholar 

  12. Giraudo, C.G. et al. J. Biol. Chem. 283, 21211–21219 (2008).

    CAS  Article  Google Scholar 

  13. Malsam, J. et al. Proc. Natl. Acad. Sci. USA 106, 2001–2006 (2009).

    CAS  Article  Google Scholar 

  14. Giraudo, C.G. et al. Science 323, 512–516 (2009).

    CAS  Article  Google Scholar 

  15. Lu, B., Song, S. & Shin, Y.K. J. Mol. Biol. 396, 602–609 (2010).

    CAS  Article  Google Scholar 

  16. Yang, X., Kaeser-Woo, Y.J., Pang, Z.P., Xu, W. & Sudhof, T.C. Neuron 68, 907–920 (2010).

    CAS  Article  Google Scholar 

  17. Weninger, K., Bowen, M.E., Choi, U.B., Chu, S. & Brunger, A.T. Structure 16, 308–320 (2008).

    CAS  Article  Google Scholar 

  18. Xue, M. et al. Nat. Struct. Mol. Biol. 17, 568–575 (2010).

    CAS  Article  Google Scholar 

  19. Choi, U.B. et al. Nat. Struct. Mol. Biol. 17, 318–324 (2010).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Keith R. Weninger is in the Department of Physics, North Carolina State University, Raleigh, North Carolina, USA.,

    Keith R Weninger

Authors
  1. Keith R Weninger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith R Weninger.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Weninger, K. Complexin arrests a neighbor. Nat Struct Mol Biol 18, 861–863 (2011). https://doi.org/10.1038/nsmb.2118

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.2118

Further reading

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing