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Complexin suppresses spontaneous exocytosis by capturing the membrane-proximal regions of VAMP2 and SNAP25

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-ethylmaleimi...

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Main Authors: Malsam, Jörg (Author) , Bärfuss, Simon (Author) , Trimbuch, Thorsten (Author) , Zarebidaki, Fereshteh (Author) , Sonnen, Andreas F. -P. (Author) , Wild, Klemens (Author) , Malsam, Andrea (Author) , Rohland, Lukas (Author) , Mayer, Matthias P. (Author) , Sinning, Irmgard (Author) , Briggs, John A. G. (Author) , Rosenmund, Christian (Author) , Söllner, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 21 July 2020
In: Cell reports
Year: 2020, Volume: 32, Issue: 3, Pages: 107926
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107926
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2020.107926
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124720309074
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Author Notes:Jörg Malsam, Simon Bärfuss, Thorsten Trimbuch, Fereshteh Zarebidaki, Andreas F.-P. Sonnen, Klemens Wild, Andrea Scheutzow, Lukas Rohland, Matthias P. Mayer, Irmgard Sinning, John A.G. Briggs, Christian Rosenmund, Thomas H. Söllner
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Summary: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.
Item Description:Gesehen am 26.10.2020
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107926

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