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Munc18-1 and Syntaxin1: Unraveling the Interactions Between the Dynamic Duo

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Abstract

All neurotransmitter and hormone regulated secretory events involve the action of three soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, syntaxin, SNAP-25, and synaptobrevin. The SNARE proteins interact to form a four alpha-helical complex, involving syntaxin and SNAP-25 on the plasma membrane and synaptobrevin on the vesicular membrane, bringing the opposing membranes together, promoting bilayer merger and membrane fusion. The process of regulated secretion is an adaptation of the membrane fusion events which occur at multiple steps throughout the intracellular trafficking pathway, in each case catalyzed by SNARE protein isoforms. At all of these locations, the SNAREs are joined by a member of the Sec1p/Munc18 (SM) protein family which selectively bind to syntaxin isoforms. From their initial identification, the SM proteins were known to be essential for membrane fusion, however, over the intervening decades, deciphering the precise mechanism of action of the SM proteins has proved problematic. Recent studies, investigating the interactions of munc18-1 and syntaxin1, provide an explanation for previous, apparently conflicting, observations yielding a new understanding of their cellular functions.

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Acknowledgments

We would like to thank both the Medical Research Council and Wellcome Trust for their funding.

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Authors and Affiliations

  1. Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh, EH8 9XD, UK

    Annya M. Smyth & Rory R. Duncan

  2. Department of Chemistry, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK

    Colin Rickman

Authors
  1. Annya M. Smyth
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  2. Rory R. Duncan
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  3. Colin Rickman
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Correspondence to Colin Rickman.

Additional information

A commentary to this article can be found at doi:10.1007/s10571-010-9610-0.

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Smyth, A.M., Duncan, R.R. & Rickman, C. Munc18-1 and Syntaxin1: Unraveling the Interactions Between the Dynamic Duo. Cell Mol Neurobiol 30, 1309–1313 (2010). https://doi.org/10.1007/s10571-010-9581-1

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