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  Complexin Suppresses Spontaneous Exocytosis by Capturing the Membrane-Proximal Regions of VAMP2 and SNAP25

Malsam, J., Barfuss, S., Trimbuch, T., Zarebidaki, F., Sonnen, A. F. P., Wild, K., et al. (2020). Complexin Suppresses Spontaneous Exocytosis by Capturing the Membrane-Proximal Regions of VAMP2 and SNAP25. Cell Reports, 32(3): 107926. doi:10.1016/j.celrep.2020.107926.

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 Creators:
Malsam, J., Author
Barfuss, S., Author
Trimbuch, T., Author
Zarebidaki, F., Author
Sonnen, A. F. P., Author
Wild, K., Author
Scheutzow, A., Author
Rohland, L., Author
Mayer, M. P., Author
Sinning, I., Author
Briggs, John A. G.1, 2, Author              
Rosenmund, C., Author
Sollner, T. H., Author
Affiliations:
1European Molecular Biology Laboratory, External Organizations, ou_3346677              
2MRC Laboratory of Molecular Biology, External Organizations, Cambridge, GB, ou_3346673              

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Free keywords: spontaneous neurotransmitter release snare complex synaptotagmin-i 3-dimensional structure phospholipid-binding molecular-mechanisms synaptic exocytosis docked vesicles accessory helix ribbon synapses Cell Biology
 Abstract: The neuronal protein complexin contains multiple domains that exert clamping and facilitatory functions to tune spontaneous and action potential-triggered synaptic release. We address the clamping mechanism and show that the accessory helix of complexin arrests assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that forms the core machinery of intracellular membrane fusion. In a reconstituted fusion assay, site- and stage-specific photo-cross-linking reveals that, prior to fusion, the complexin accessory helix laterally binds the membrane-proximal C-terminal ends of SNAP25 and VAMP2, Corresponding complexin interface mutants selectively increase spontaneous release of neurotransmitters in living neurons, implying that the accessory helix suppresses final zippering/assembly of the SNARE four-helix bundle by restraining VAMP2 and SNAP25.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: WOS:000552075500018
DOI: 10.1016/j.celrep.2020.107926
ISSN: 2211-1247
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Title: Cell Reports
  Alternative Title : Cell Reports
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 32 (3) Sequence Number: 107926 Start / End Page: - Identifier: -