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: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
21 July 2020
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| 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 
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| 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 |
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| 245 | 1 | 0 | |a Complexin suppresses spontaneous exocytosis by capturing the membrane-proximal regions of VAMP2 and SNAP25 |c 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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| 520 | |a 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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