Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission
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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.
Original language | English |
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Journal | Neuron |
Volume | 95 |
Issue number | 6 |
Pages (from-to) | 1350-1364 |
Number of pages | 15 |
ISSN | 0896-6273 |
DOIs | |
Publication status | Published - 2017 |
Externally published | Yes |
Bibliographical note
Copyright © 2017 Elsevier Inc. All rights reserved.
- Animals, Carrier Proteins/metabolism, Drosophila, Exocytosis/physiology, Neuromuscular Junction/metabolism, Synaptic Transmission/physiology, Synaptic Vesicles/metabolism
Research areas
ID: 334034941