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Cell Rep. 2018 May 1;23(5):1259-1274. doi: 10.1016/j.celrep.2018.03.126.

Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses.

Author information

1
Institute for Biology/Genetics, Freie Universität Berlin, 14195 Berlin, Germany.
2
Max Planck Institute of Psychiatry, 80804 Munich, Germany; Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
3
German Center for Neurodegenerative Disorders, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
4
Institute for Biology/Genetics, Freie Universität Berlin, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin, 10117 Berlin, Germany; Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
5
Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA.
6
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
7
NeuroCure Cluster of Excellence, Charité Universitätsmedizin, 10117 Berlin, Germany; Institut für Neurophysiologie, Charité Universitätsmedizin, 10117 Berlin, Germany.
8
Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA. Electronic address: katherine.nagel@nyumc.org.
9
Institute for Biology/Genetics, Freie Universität Berlin, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin, 10117 Berlin, Germany. Electronic address: stephan.sigrist@fu-berlin.de.

Abstract

High-throughput electron microscopy has started to reveal synaptic connectivity maps of single circuits and whole brain regions, for example, in the Drosophila olfactory system. However, efficacy, timing, and frequency tuning of synaptic vesicle release are also highly diversified across brain synapses. These features critically depend on the nanometer-scale coupling distance between voltage-gated Ca2+ channels (VGCCs) and the synaptic vesicle release machinery. Combining light super resolution microscopy with in vivo electrophysiology, we show here that two orthogonal scaffold proteins (ELKS family Bruchpilot, BRP, and Syd-1) cluster-specific (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from VGCCs across synapses of the Drosophila olfactory system, resulting in different synapse-characteristic forms of short-term plasticity. Moreover, BRP/Unc13A versus Syd-1/Unc13B ratios were different between synapse types. Thus, variation in tightly versus loosely coupled scaffold protein/(M)Unc13 modules can tune synapse-type-specific release features, and "nanoscopic molecular fingerprints" might identify synapses with specific temporal features.

KEYWORDS:

Bruchpilot; Drosophila; Syd-1; active zone; munc13; nanoscopy; neurotransmitter release; olfactory system; positional priming; synapse diversity; synapse physiology

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