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, Thorsten; 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/persons50431

Mielke, Thorsten
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, 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)

Reddy-Alla.pdf
(Publisher version), 6MB

Supplementary Material (public)

There is no public supplementary material available

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/21.11116/0000-0003-56D8-9

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.