Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission
2017-09-13 | journal article
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Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission
Reddy-Alla, S.; Böhme, M.; Reynolds, E.; Beis, C.; Grasskamp, A. T.; Mampell, M. M. & Maglione, M. et al. (2017)
Neuron, 95(6) pp. 1350-1364. DOI: https://doi.org/10.1016/j.neuron.2017.08.016
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Details
- Authors
- Reddy-Alla, Suneel; Böhme, Mathias; Reynolds, Eric; Beis, Christina; Grasskamp, Andreas T.; Mampell, Malou M.; Maglione, Marta; Jusyte, Meida; Rey, Ulises; Babikir, Husam; McCarthy, Anthony W.; Quentin, Christine; Matkovic, Tanja; Bergeron, Dominique Dufour; Mushtaq, Zeeshan; Göttfert, Fabian ; Owald, David; Mielke, Thorsten; Walter, Alexander M.
- Abstract
- Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging of Drosophila neuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release.
- Issue Date
- 13-September-2017
- Journal
- Neuron
- eISSN
- 1097-4199
- Language
- English