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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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Hauptverfasser: Malsam, Jörg (VerfasserIn) , Bärfuss, Simon (VerfasserIn) , Trimbuch, Thorsten (VerfasserIn) , Zarebidaki, Fereshteh (VerfasserIn) , Sonnen, Andreas F. -P. (VerfasserIn) , Wild, Klemens (VerfasserIn) , Malsam, Andrea (VerfasserIn) , Rohland, Lukas (VerfasserIn) , Mayer, Matthias P. (VerfasserIn) , Sinning, Irmgard (VerfasserIn) , Briggs, John A. G. (VerfasserIn) , Rosenmund, Christian (VerfasserIn) , Söllner, Thomas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 July 2020
In: Cell reports
Year: 2020, Jahrgang: 32, Heft: 3, Pages: 107926
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107926
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2020.107926
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124720309074
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 26.10.2020
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.107926

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