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.; Maglione, M.; Jusyte, M.; Rey, U.; Babikir, H.; McCarthy, A. W.; Quentin, C.; Matkovic, T.; Bergeron, D. D.; Mushtaq, Z.; Göttfert, F.; Owald, D.; Mielke, T.; Hell, S. W.; Sigrist, S. J.; Walter, A. M.

doi:10.1016/j.neuron.2017.08.016

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Stable positioning of Unc13 restricts synaptic vesicle fusion to defined release sites to promote synchronous neurotransmission.

MPS-Authors

/persons/resource/persons96560

Göttfert, F.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons15210

Hell, S. W.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

2477083_Suppl_1.pdf
(Supplementary material), 2MB

2477083_Suppl_2.xlsx
(Supplementary material), 84KB

2477083_Suppl_3.mp4
(Supplementary material), 9MB

2477083_Suppl_4.pdf
(Supplementary material), 8MB

Citation

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.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-E274-A

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.