Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses

• Published in: Cell reports (Cambridge) 2018-05, Vol.23 (5), p.1259-1274
• Main Authors: Fulterer, Andreas, Andlauer, Till F.M., Ender, Anatoli, Maglione, Marta, Eyring, Katherine, Woitkuhn, Jennifer, Lehmann, Martin, Matkovic-Rachid, Tanja, Geiger, Joerg R.P., Walter, Alexander M., Nagel, Katherine I., Sigrist, Stephan J.
• Format: Article
• Language: English
• Subjects: active zone; Animals; Bruchpilot; Drosophila; Drosophila melanogaster; Drosophila Proteins - metabolism; GTPase-Activating Proteins - metabolism; Membrane Proteins - metabolism; munc13; Mushroom Bodies - metabolism; Mushroom Bodies - ultrastructure; nanoscopy; Nerve Tissue Proteins - metabolism; neurotransmitter release; olfactory system; positional priming; Syd-1; synapse diversity; synapse physiology; Synaptic Vesicles - metabolism; Synaptic Vesicles - ultrastructure
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.03.126

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. [Display omitted] •Active zone scaffold proteins systematically differ between synapse types in Drosophila•BRP localizes Unc13A 30–40 nm closer to voltage-gated Ca2+ channels than Syd-1 Unc13B•BRP/Unc13A dominates at fast, depressing, Syd-1/Unc13B at slow, facilitating synapses Fulterer et al. demonstrates that the scaffold proteins Bruchpilot and Syd-1 cluster (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from voltage-gated Ca2+ channels in the Drosophila olfactory system. These scaffold/release factor “modules” varied significantly between different synapse types, thereby tuning release features toward depression or facilitation.