Journal
NEURON
Volume 95, Issue 6, Pages 1350-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2017.08.016
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [Exc 257, TP A3, A6 SFB958, TP B9/SFB665, TP09, TPZ1, SFB740]
- A.M. Walter [TRR186]
- DFG [Exc 257, GRK 1123, SFB 740]
- International Max Planck Research School (IMPRS)
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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.
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