Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses

Research output: Contribution to journalJournal articleResearchpeer-review

  • Andreas Fulterer
  • Till F M Andlauer
  • Anatoli Ender
  • Marta Maglione
  • Katherine Eyring
  • Jennifer Woitkuhn
  • Martin Lehmann
  • Tanja Matkovic-Rachid
  • Joerg R P Geiger
  • Walter, Alexander Matthias
  • Katherine I Nagel
  • Stephan J Sigrist

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.

Original languageEnglish
JournalCell Reports
Volume23
Issue number5
Pages (from-to)1259-1274
Number of pages16
ISSN2211-1247
DOIs
Publication statusPublished - 1 May 2018
Externally publishedYes

Bibliographical note

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

    Research areas

  • Animals, Drosophila Proteins/metabolism, Drosophila melanogaster, GTPase-Activating Proteins/metabolism, Membrane Proteins/metabolism, Mushroom Bodies/metabolism, Nerve Tissue Proteins/metabolism, Synaptic Vesicles/metabolism

ID: 334034215