FMP Publications

Our publications are recorded in a searchable database since 2010, updates will be added regularly.

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References
Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca(2+) channel-vesicle coupling
Böhme(*), M. A., Beis(*), C., Reddy-Alla(*), S., Reynolds(*), E., Mampell(*), M. M., Grasskamp, A. T., Lutzkendorf(*), J., Bergeron(*), D. D., Driller(*), J. H., Babikir(*), H., Göttfert(*), F., Robinson(*), I. M., O'Kane(*), C. J., Hell(*), S. W., Wahl(*), M. C., Stelzl(*), U., Loll(*), B., Walter, A. M.; Sigrist(*), S. J.
Nat Neurosci, 19:1311-1320
(2016)

Tags: Molecular and Theoretical Neuroscience (Walter)

Abstract: Brain function relies on fast and precisely timed synaptic vesicle (SV) release at active zones (AZs). Efficacy of SV release depends on distance from SV to Ca(2+) channel, but molecular mechanisms controlling this are unknown. Here we found that distances can be defined by targeting two unc-13 (Unc13) isoforms to presynaptic AZ subdomains. Super-resolution and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-alpha, and Unc13A was positioned by Bruchpilot and Rim-binding protein complexes at maturing AZs. Unc13B localized 120 nm away from Ca(2+) channels, whereas Unc13A localized only 70 nm away and was responsible for docking SVs at this distance. Unc13A(null) mutants suffered from inefficient, delayed and EGTA-supersensitive release. Mathematical modeling suggested that synapses normally operate via two independent release pathways differentially positioned by either isoform. We identified isoform-specific Unc13-AZ scaffold interactions regulating SV-Ca(2+)-channel topology whose developmental tightening optimizes synaptic transmission.

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Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)
info(at)fmp-berlin.de

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