Ca2+-Triggered Synaptic Vesicle Fusion Initiated by Release of Inhibition. Issue 8 (August 2018)

• Record Type: Journal Article
• Authors: Brunger, Axel T.; Leitz, Jeremy; Zhou, Qiangjun; Choi, Ucheor B.; Lai, Ying
• Is Part Of: Trends in cell biology. Volume 28:Issue 8(2018)
• Page Start: 631
• Page End: 645
• Publication Date: 2018-08
• Subjects: action potential -- Ca2+ triggering -- fusion protein -- synaptic vesicle fusion -- synaptic vesicle priming; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2018.03.004
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Recent structural and functional studies of the synaptic vesicle fusion machinery suggest an inhibited tripartite complex consisting of neuronals oluble N -ethylmaleimide sensitive factora ttachment proteinre ceptors (SNAREs), synaptotagmin, and complexin prior to Ca 2+ -triggered synaptic vesicle fusion. We speculate that Ca 2+ -triggered fusion commences with the release of inhibition by Ca 2+ binding to synaptotagmin C2 domains. Subsequently, fusion is assisted by SNARE complex zippering and by active membrane remodeling properties of synaptotagmin. This additional, inhibitory role of synaptotagmin may be a general principle since other recent studies suggest that Ca 2+ binding to extended synaptotagmin C2 domains enables lipid transport by releasing an inhibited state of the system, and that Munc13 may nominally be in an inhibited state, which is released upon Ca 2+ binding to one of its C2 domains. Highlights: The recent structure of the prefusion complex of neuronal SNAREs, complexin-1, and synaptotagmin-1, along with functional studies, suggests that Ca 2+ -triggered fusion is initiated by release of inhibition. Activating properties, such as full zippering of the SNARE complex, synaptotagmin-induced membrane bending, or membrane bridging, would act after the release of inhibition. Inhibitory properties of synaptotagmin C2 domains at the resting level of Ca 2+ have also been suggested to occur for extended synaptotagmins and Munc13.