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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. A., Reynolds, E., Beis, C., Grasskamp, A. T., Mampell, M. M., et al. (2017). Stable positioning of Unc13 restricts synaptic vesicle fusion to defined release sites to promote synchronous neurotransmission. Neuron, 95(6), 1350-1364. doi:10.1016/j.neuron.2017.08.016.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-E274-A Version Permalink: http://hdl.handle.net/21.11116/0000-0001-485D-7
Genre: Journal Article

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 Creators:
Reddy-Alla, S., Author
Böhme, M. A., Author
Reynolds, E., Author
Beis, C., Author
Grasskamp, A. T., Author
Mampell, M. M., Author
Maglione, M., Author
Jusyte, M., Author
Rey, U., Author
Babikir, H., Author
McCarthy, A. W., Author
Quentin, C., Author
Matkovic, T., Author
Bergeron, D. D., Author
Mushtaq, Z., Author
Göttfert, F.1, Author              
Owald, D., Author
Mielke, T., Author
Hell, S. W.1, Author              
Sigrist, S. J., Author
Walter, A. M., Author more..
Affiliations:
1Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

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Free keywords: synapse; Unc13; scaffolding proteins; active zone; release site; STED microscopy; local synaptic activity imaging; in vivo imaging; variance-mean analysis; high-pressure freeze electron microscopy
 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.

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Language(s): eng - English
 Dates: 2017-08-312017-09-13
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.neuron.2017.08.016
 Degree: -

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Title: Neuron
Source Genre: Journal
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Pages: - Volume / Issue: 95 (6) Sequence Number: - Start / End Page: 1350 - 1364 Identifier: -